摘要:

9 Synthetic Methods By N.J. LAWRENCE Department of Chemistry UMIST PO Box 88 Manchester M60 1QD UK 1 Introduction A noticeable recent trend in organic chemistry which has continued this year has been the development of cleaner synthetic methods and technologies to meet ever stricter environmental regulations and of course for economic reasons. This has led to an increase in reports detailing asymmetric catalysis and selective syntheses. On the other hand there have been many reports of deliberately unselective syntheses. Such research driven by the pharmaceutical industry in the search for new therapeutic leads has stimulated many new approaches to the synthesis of libraries of small organic molecules.'.2 The year has seen disclosure of many new catalytic less toxic milder and cleaner methods that replace older less environmentally friendly protocols.For example an interesting article detailing photochemical syntheses with sunlight has a~peared.~ The year saw an intriguing publication claiming the efficient asymmetric reduction of ketones when the reaction was performed in a static magnetic field.4 Had the observation proved correct asymmetric synthesis could have been revolutionized. However so important were the claims that several group^^.^ were quick in attempting to reproduce the results but alas without success. The paper was shown to be in error and fully retracted. Many natural products have succumbed to total synthesis this year. Perhaps the most publicized has been the total synthesis of paclitaxel (Ta~ol),~ finally achieved by the groups of Nicolaou' and H01ton.~ Other impressive total syntheses include those of T.Carell E.A. Wintner A. Bashir-Hashemi and J. Rebek Jr. Angew. Chem. Int. Ed. Engl. 1994,33,2059. C. X. Chen L. A. A. Randall R. B. Miller A. D. Jones and M. J. Kurth J. Am. Chem. SOC.,1994,116,2661. P. Esser B. Pohlmann and H.-D. Scharf Angew. Chem. Znt. Ed. Engl. 1994 33 2009. G. Zadel C. Eisenbraun G. J. Wolff and E. Breitmaier Angew. Chem. Int. Ed. Engl. 1994 33 454. B. L. Feringa R. M. Kellogg R. Hulst C. Zondervan and W. H. Kruizinga Angew. Chem. Int. Ed. Engl. 1994 33 1458. G. Kaupp and T. Marquardt Angew. Chem. Int. Ed. Engl. 1994 33 1459. ' K. C. Nicolaou W.-M. Dai R.K. Guy Angew. Chem. Int. Ed. Engl. 1994,33 15; A. N.Boa P. R. Jenkins and N. J. Lawrence Contemp. Org. Synth. 1994 1 47. K. C. Nicolaou Z. Yang J. J. Liu H. Ueno P.G. Nantermet R. K. Guy C. F. Claiborne J. Renaud E. A. Couladouros K. Paulvannan and E. J. Sorensen Nature(London) 1994 367 630. For a review of this synthesis see S. B. Horwitz Nature(London) 1994 367 593. R. A. Holton C. Somoza H.-B. Kim F. Liang R. J. Biediger P. D. Boatman M. Shindo C. C. Smith S. C. Kim H. Nadizadeh Y. Suzuki C. L. Tao P. Vu S. H. Tang P.S. Zhang K. M. Murthi L.N. Gentile and J. H. Liu J. Am. Chem. SOC.,1994,116 1597; R. A. Holton H.-B. Kim C. Somoza F. Liang R. J. Biediger P. D. Boatman M. Shindo,C. C. Smith S.C. Kim H. Nadizadeh Y. Suzuki C. L. Tao P. Vu S. Tang P. S. Zhang K. M. Murthi L.N. Gentile and J. H. Liu J. Am.Chem. SOC. 1994,116 1599. For a review of this synthesis see L. Wessjohann Angew. Chem. Int. Ed. Engl. 1994 33 959. 289 290 N. J. Lawrence bleomycin A2,10 (-j-calyculin A," zaragozic acid A,12 and calicheamicin y\.13 With the impressive current state of natural product synthesis how long will it be before maitotoxin the most toxic and largest known non-biopolymer natural product structurally determined this year,I4 has succumbed to total synthesis? 0 OH I' BzO AcO Paclitaxel 0 OAc Zaragozic acid A Specialist reference works that have been published this year include Volumes 45' and 4616 of Organic Reactions which review the Nazarov cyclization,"" ketene cyclizations,llb the use of tin@) enolates in the aldol Michael and related reactions,'2a the [2,3] Wittig reaction,' 2b and reductions with samarium(I1) iodide;I2' Fieser and Fieser's 'Reagents for Organic Synthesis' Volume 17;17 and two Tetrahedron symposia-in-print describing synthetic methods 'Palladium in Organic Synthesis'I8 and 'Catalytic Asymmetric Addition Reactions'.l9 Two Tetrahedron Reports describe synthetic methods 'Opportunities in Asymmetric Synthesis An Industrial Prospect',20 and 'Recent Developments in the Stereoselective Synthesis of a-Amino Acids'.21 Books published this year describing synthetic methods include works describing asymmetric catalysi~;~~.~~ stereoselective 10 D. L. Boger and T. Honda J. Am. Chem. Soc. 1994 116 5647 and preceding papers. 11 N. Tanimoto S. W. Gerritz A. Sawabe T.Noda S.A. Filla and S. Masamune Angew. Chem. Int. Ed. Engl. 1994 33 673. 12 K. C. Nicolaou A. Nadin J. E. Leresche E. W. Yue and S. La Greca Angew. Chem. Int. Ed. Engl. 1994,33 2190. 13 S.A. Hitchcock S. H. Boyer M. Y. Chumoyer S. H. Olson and S.J. Danishefsky Angew. Chem. Int. Ed. Engl. 1994 33 858. 14 M. Murata H. Naoki S. Matsunaga M. Satake and T. Yasumoto J. Am. Chem. SOC. 1994 116 7098. I5 (a)K. L. Habermas S. E. Denmark and T. K. Jones Org. React. (N. Y.),1994,451; (b)J. Hyatt and P. W. Raynolds ibid 1994 45 159. 16 (a)T. Mukaiyama and S. Kobayashi Org. React. (N.Y.),1994 46 1; (h)T. Nakai and K. Mikami ibid. 1994 46 105; (c)G. Molander ibid. 1994 46 211. 17 M. Fieser 'Reagents for Organic Synthesis' Wiley New York 1994 Vol. 17. 18 Tetrahedron 1994 50 285.19 Tetrahedron 1994 50 4235. 20 S. Kotha Tetrahedron 1994 50 3639. 21 R. 0.Duthaler Tetrahedron 1994 50 1539. 22 Ryoji Noyori 'Asymmetric Catalysis in Organic Synthesis' Wiley New York 1994. 23 'Catalysis of Organic Reactions' ed. J. R. Kosak and T. A. Johnson Dekker New York 1994. Synthetic Methods 29 1 Scheme 1 synthesi~;~~*~~ electrochemistry;26 enzymes;27 organosulfur,28 organoiron2’ or-gan~lanthanide,~’ compounds; named organic reactions;33 and ~rganometallic~’.~~ and organic synthesis.34 2 Carbon-Carbon Bond Formation The asymmetric addition of organometallic reagents to carbonyl compounds has been the focus of many reports this year. Corey and Cimprich have described the synthesis of alkynylalcohols (3) using chiral oxazaborolidines as catalysts for the enantioselective addition of alkynyl boranes (1)to aldehydes (Scheme 1).35The process is analogous to the asymmetric reduction of ketones with boranes and the same oxazaborolidine catalysts.The alkynylborane (2) is derived from bromodimethylborane and an alkynyltributylstannane and used without isolation. Excellent yields and enantiomeric excesses are obtained with the oxazaborolidine (4). The transition-state model (5)can account for the stereoselectivity observed. The two phenyl substituents shield the top 24 Atta-ur-Rahman and Z. Shah ‘Stereoselective Synthesis in Organic Chemistry’ Springer-Verlag New York 1994. 25 ‘Stereoselective Synthesis Lectures Honouring Rudolf Wiechert’ ed. E.Ottow K. Schollkopf and B. G. Schulz Springer-Verlag New York 1994. 26 Frantisek Liska ‘Electrochemistry in Organic Synthesis’ Springer-Verlag New York 1994. ” C. H. Wong and G. M. Whitesides ‘Enzymes in Synthetic Organic Chemistry’ Tetrahedron Organic Chemistry Series uol. 12 Elsevier Oxford 1994. ‘Sulfur Reagents in Organic Synthesis’ ed. P. Metzner and A. Thuillier Best Synthetic Methods Series Academic Press 1994. 29 ‘Iron Compounds in Organic Synthesis’ ed. A. J. Pearson Best Synthetic Methods Series Academic Press London 1994. 30 Tsuneo Imamoto ‘Lanthanides in Organic Synthesis’ Best Synthetic Methods Series Academic Press London 1994. 31 ‘Organometallic Reagents in Organic Synthesis’ ed. J. H. Bateson and M. B. Mitchell Academic Press London 1994.32 ‘Organometallics in Synthesis A Manual’ ed. Manfred Schlosser John Wiley & Sons Chichester 1994. 33 A. Hassner and C. Stumer ‘Organic Syntheses Based on Name Reactions and Unnamed Reactions’ Tetrahedron Organic Chemistry Series Elsevier 1994. 34 M. Smith ‘Organic Synthesis’ McGraw-Hill New York 1994. 35 E.J. Corey and K.A. Cimprich J. Am. Chem. Soc. 1994 116 3151. N. J. Lawrence (6) 2 moPh; 94% 8.8. (7) 5 md%; 96% 8.8. Figure 1 Selectivity in the addition of ZnEt to PhCHO face of the oxazaborolidine ring promoting coordination of both the aldehyde and the alkynylborane from the lower face. Additionally the butyl group and the aldehyde hydrogen atom are oriented syn. Subsequent intramolecular delivery of the alkynyl group occurs to the re face of the aldehyde and also releases the oxazaborolidine (4) which re-enters the catalytic cycle.The alkynyl tin reagents used in this new method can be accessed from alkynyl silicon reagents by a new method described by Buchwald . The asymmetric catalytic addition of organozinc reagents to aldehydes has proved as popular as ever this year (Figure 1). Some of the catalysts used include the thiolate (6)in combination with zinc chloride37 and the carbohydrate derivative (7).38Most of the catalysts of this type of reaction are used in combination with diethylzinc. However Soai et aL3' have shown that many N,N-dialkylnorephedrine catalysts are able to deliver an isopropyl group from diisopropylzinc a commercially available reagent. Eisenberg and Knochel have also used this type of chemistry to make chiral 1,2-diols.The diols are made by asymmetric addition of diorganozinc reagents to or-trialkyl- ~iloxyaldehydes.~~ The first examples of enantioselective nucleophilic trifluoromethylation of carbonyl compounds have been disclosed by Iseki et al. using a different organometallic reagent presumably a silicate species. They have shown that trifluoromethyltrimethylsilane adds cleanly to both aldehydes and ketones in the presence of the chiral quaternary ammonium fluoride (8) albeit in modest optical yield (Scheme 2a).41 A variant of the reaction of an organometallic reagent with a ketone has been reported by Kim et al. They have developed a potentially useful method for transforming a ketone to a gem-dimethyl group (9) t(lo) by the use of trimethylaluminium and trimethylsilyl triflate (Scheme 2b).42 The asymmetric allylation of aldehydes is normally best achieved by using a chiral Lewis acid.Denmark et al. have approached this transformation somewhat different- ly.43 They have shown that asymmetric allylation and crotonylation of aldehydes (11) -,(12) occurs in high yield and moderate enantioselectivity when the reaction is promoted by a chiral Lewis base. They found that the chiral base (13) in combination with trichloroallylsilanes gave the best results (Scheme 3a). The reaction is thought to 36 B.P. Warner and S. L. Buchwald J. Org. Chem. 1994 59 5822. 37 E. Rijnberg J. T. B. H. Jastrzebski M. D. Janssen,J. Boersma and G. van Koten Tetrahedron Lett.1994 35 6521. B.T. Cho and N. Kim Tetrahedron Lett. 1994 35 41 15. 39 K. Soai T. Hayase K. Takai and T. Sugiyama J. Org. Chem. 1994 59 7908. 40 C. Eisenberg and P. Knochel J. Org. Chem. 1994 59 3760. 41 K. Iseki T. Nagai and Y. Kobayashi Tetrahedron Lett. 1994 35 3137. 42 C.U. Kim P.F. Misco B.Y. Luh and M.M. Mansuri Tetrahedron Lett. 1994 35 3017. 43 S.E. Denmark D. M. Coe N. E. Pratt and B. D. Griedel J. Org. Chem. 1994 59 6161. Synthetic Methods Scheme 2 Me A :i Pd(PPh3),; ii Etgn cyclohexanone B :i Cycbhexanone; ii,Sml (b) Scheme 3 proceed via a closed transition state involving a hexacoordinate siliconate species. Allylation of aldehydes and ketones can also be achieved with allylic sulfones using two new methods from the Julia group.The first method (A)44 involves the reduction of the sulfone with diethylzinc catalysed by palladium(o) giving a nucleophilic species which reacts in situ with ketones. The second method (B) involves the use of samarium(I1) iodide (Scheme 3b).45 Denmark et al. have described the asymmetric addition of organolithium reagents to imine~.~~ Addition of methyllithium to the p-methoxyphenyl imine (14) is highly enantioselective when catalysed by the L-t-leucinol-derived bis-oxazoline ligand (1 5)or ( -)-sparteine (16) (Scheme 4a). The enantioselectivity is only slightly reduced when only 0.1 equivalent of the ligand is used. In a different type of reaction (-)-sparteine has also been used to control the enantioselective alkylation of racemic organolithium 44 J.Clayden and M. Julia J. Chem. Soc. Chem. Commun. 1994 1905. 45 J. Clayden and M. Julia J. Chem. Soc. Chem. Commun. 1994 2261. 46 S.E. Denmark N. Nakajima and 0.J.-C. Nicaise J. Am. Chem. Soc. 1994 116 8797. 294 N. J. Lawrence reagents.47 Treatment of benzamide (17) with s-butyllithium/( -)-sparteine (16) gives the benzyllithium/sparteine complex (18) which upon reaction with Bu"0Ts gives the alkylated product (19) with impressive enantioselectivity (Scheme 4b). An intriguing feature of this reaction is the reversal of enantioselectivity upon changing the leaving group from tosyl to chloride (%YO 8OY0e.e.). A similar process the catalytic asymmetric alkylation of enolates has long been a major goal of organic synthesis e.g.(20) + (21). Koga and coworkers48 have achieved this goal using the ligand (22) which effects the asymmetric benzylation of achiral lithium enolates. The lithium enolate (20) (from the corresponding silyl enol ether and MeLi-LiBr) gave the alkylated product (21) with (22) as a catalyst in the presence of diamine (23) which functions as a scavenger of the lithium bromide (Scheme 4c). The design of new chiral auxiliaries for asymmetric C-C bond formation has featured prominently in 1994. Commins et al. have developed the new auxiliary (25) as an alternative to the widely used but expensive 8-phenylmenth01.~~ It is prepared efficiently from inexpensive limonene oxide (24) (available as a cisltrans mixture). The chiral oxazolidinone (26),50 a Diels-Alder adduct of 2-oxazolone the camphene- derived oxazolidinone (27),5 and the 2-amino-3-borne01 derived (28)52 are useful new Evans-like auxiliaries for asymmetric alkylation conjugate addition and Diels-Alder reactions.Davies et al. have found that derivatives of 3,3-dimethyl-2-pyrrolidinone (29)-so-called quatsS3-act in a similar fashion to oxazolidinone auxiliaries enabling impressive asymmetric aldol and alkylation reaction^.'^ Another Evans-like protocol involves the use of pseudoephedrine as an auxiliary for enolate asymmetric alkylati~n.'~ Alkylation of the dianion of the amide (30) occurs with exceptionally high diastereoselectivity to give pseudoephedrine amides (3 1) that function directly as precursors to acids alcohols aldehydes and ketones by treatment with sulfuric acid borane-lithium pyrrolidide triethoxyaluminium hydride and alkyllithium reagents respectively (Scheme 6).Ley and coworkerP have used dispiroacetals groups57 effectively as chiral auxiliaries. The alkylation of the protected lactate (32) +(33) is highly stereoselective; the overall process is similar to Seebach's self-reproduction of chirality. In addition glycolate dispiroketals made from a chiral bis(dihydropyran) are alkylated with high stereoselectivity. The chiral C,-symmetric dispiroketal (34) is just one of a range of diolsS8 made by the Ley group that have been used as chiral auxiliaries (Scheme 7). The diacryloyl and dicrotonyl esters of (34) show excellent diastereoselectivity in Diels-AlderS9 and conjugate addition6' reactions.The chiral ferrocenyldiphosphine 47 S. Thayurnanavan S. Lee C. Liu and P. Beak J. Am. Chem. SOC. 1994 116 9755. 48 M. Irnai A. Hagihara H. Kawasaki K. Manabe and K. Koga J. Am. Chem. SOC. 1994 116 8829. 49 D. L. Cornrnins L. G.-Weltzien and J. M. Salvador SYNLETT 1994 972. 50 N. Hashirnoto T. Ishizuka and T. Kunieda Tetrahedron Lett. 1994 35 721. 51 M.R. Banks A.J. Blake A.R. Brown J.I.G. Cadogan S. Gaur I. Gosney P.K.G. Hodgson and P. Thorburn Tetrahedron Lett. 1994 35 489. 52 C. Palorno F. Berree A. Linden and J. M. Villalgordo J. Chem. SOC.,Chem. Commun. 1994 1861. 53 S.G. Davies G.J.-M. Doisneau J.C. Prodger and H. J. Sanganee Tetrahedron Lett. 1994 35 2369. 54 S.G. Davies G. J.-M. Doisneau J. C. Prodger and H. J.Sanganee Tetrahedron Lett. 1994 35 2373. 55 A.G. Meyers B. H. Yang H. Chen and J. L. Gleason J. Am. Chem. SOC. 1994 116 9361. R. Downharn K. S. Kim S. V. Ley and M. Woods Tetrahedron Lett. 1994 35 769. 57 T. Ziegler Angew. Chem. Int. Ed. Engl. 1994 33 2272. B.C. B. Bezuidenhoudt G. H. Castle and S.V. Ley Tetrahedron Lett. 1994 35 7447. 59 B. C. B. Bezuidenhoudt G. H. Castle J. V. Geden and S. V. Ley Tetrahedron Lett. 1994 35 7451. 6o G. H. Castle and S. V. Ley Tetrahedron Lett. 1994 35 7455. Synthetic Methods Ph-AN P "Y (15) BU' I Ph-Me 96% 91%e.e. with (15) (1 eq.) 71% 72% e.e. with (16) (1 eq.) H PizNYo (18) (19) 52% 97%e.e LiBr (20) 83% 92 % e.e. with 0.2 eq. (22) Ph 76% 96 % e.e. with 0.05 eq. (22) Scheme 4 ligand (35) is an excellent catalyst for a number of processes including enantioselective hydrogenation allylic alkylation and hydroboration.61 Aziridines62 have also been used as auxiliaries.Tanner et a!. have used the C,-symmetric bis(aziridine) (36)to effect asymmetric palladium-mediated allylic substitution dihydroxylation aziridination and cyclopropanation reactions.63 Hydrazones derived from the N-aminoaziridine (37) are alkylated with excellent diastereoselectivity in analogy with the Enders' SAMP/R AMP h ydrazones .64 61 A. Togni,C.Breutel A. Schnyder F. Spindler H. Landert and A. Tijani,J. Am. Chem.Soc.,1994,116,4062. 62 D. Tanner Angew. Chem. Int. Ed. Engl. 1994 33 599. 63 D. Tanner P.G. Anderson A. Harden and P. Somfai Tetrahedron Lett. 1994 35 4631.64 D. J. Augeri and A. R. Chamberlin Tetrahedron Lett. 1994 35 5599. N. J. Lawrence I A A (24) (25) Scheme 5 I 2 x LDA LlCl XL XicR Y R'X L -X (31) k' R >99% d.9. Scheme 6 Binaphthols commonly encountered auxiliaries and catalysts have recently been made rapidly from 2-naphthols by the action of iron(m) chloride under microwave radiation65 and by aerobic oxidation catalysed by CuCl(0H)TMEDA complex.66 (-)-2,Y-Binaphthol can be obtained stereoselectively (95% 99.5% e.e.) by the electrocatalytic oxidative coupling of 2-naphthol on a TEMPO-modified graphite felt electrode in the presence of (-)-sparteine (16).67 (_+)-2,2'-Binaphthol has been resolved in a new fashion by formation of a 1 :1 complex with N-benzylquininium chloride.* Palladium-catalysed allylic substitution of the acetate (38) with dimethyl malonate [to give (39)] is impressively enantioselective with both the aminophosphine derivatives (40)69and (41)" (Scheme 8). 65 D. Villemin and F. Sauvaget SYNLETT 1994,435. 66 M. Noji M. Nakajima and K. Koga Tetrahedron Lett. 1994 35 7983. 67 T. Osa Y. Kashiwagi Y. Yanagisawa and J. M. Bobbitt J. Chem. SOC. Chem. Commun. 1994 2535. 68 F. Toda K. Tanaka and I. Goldberg J. Org. Chem. 1994 59 5748. 69 G. Benchley E. Merifield M. Wills and M. Fedouloff Tetrahedron Lett. 1994,35 2791. 'O H. Kubota and K. Koga Tetrahedron Lett. 1994 35 6689. 297 Synthetic Methods ~ Me+% iLDNBuLi, ii PhCH,Br ph+s (32) (33)86%,d.e. > 96% Scheme 7 Ph (40)84% e.e.,(S) and (40) or (41) (38) (39) \\ (41)93% e.e.,(R) Scheme 8 Another common reaction the aldol condensation has seen chiral modification this year.The chiral tridentate ligand (44)in combination with titanium(1v) isopropoxide has been used to catalyse the asymmetric Mukaiyama aldol reaction (42) + (43).71 A similar process can be catalysed by the more conventional catalyst (R)-BINOL/TiCl (45); in this case the silyl ethers are isolated directly as the product (Scheme 9).72 Charette and Juteau have shown that the dioxaborolane (48) is an efficient chiral ligand for the asymmetric Simmons-Smith cyclopropanation of allylic alcohols e.g. (46) -,(47).73The scope of the reaction is claimed to be broad and high enantioselec- tivities are obtained with trans and cis disubstituted and trisubstituted alkenes (Scheme '' E.Carreira R. A. Singer and W.S. Lee J. Am. Chem. SOC. 1994,116 8837. 72 K. Mikami and S. Matsukawa J. Am. Chem. SOC. 1994,116 4077. 73 A. B. Charette and H. Juteau J. Am. Chem. SOC. 1994,116 2651. N. J. Lawrence Me3Si0 0 OR‘ .. H‘ (43) For (44) R = EtO R’ = H 72-98% 93% e.e. For (45) R = EtS R’ = Me,Si 60%,81% e.s. (45) (R)-BINOL-TiCI and Ti(OPi), Br Scheme 9 10a). Nishiyama et al. have developed a ruthenium-catalysed asymmetric cyclo- propanation of olefins and diaz~acetates.~~ The ligand bis(oxazoliny1)pyridine (pybox)(51) previously used as a chiral controller in ruthenium-catalysed hydrosilyla- tions is an excellent ligand in combination with [RuCl,(p-cymene)] for the asymmetric transformation (49) +(50)(Scheme lob).The same transformation can be achieved using a copper(I1)-based system and a new 1,2-diphenyl- 172-ethanediamine deri~ative.~~ Takai Utimoto and coworkers have shown that trace amounts of lead found in some samples of zinc can dramatically decrease the metal’s reactivity in the Simmons-Smith cyclopropanation of alkene~.~~ This negative effect can be suppressed simply by the addition of chlorotrimethylsilane. Kobayashi and Ishitani report an extraordinary reversal of enantioselectivity in the ‘chiral ytterbium triflate’ catalysed Diels-Alder reaction between oxazolidinone (52) and cyclopentadiene upon changing to an achiral ligand.77 Thus when cis-l,2,6- trimethylpiperidine (54) and the N-acetyloxazolidinone (55)are used as the achiral additives the enantiomer (2S,3R)-(53) is the major product.However when the achiral additives are 1,2,2,6,6-pentarnethylpiperidine (56) and diketone (57) the opposite enantiomer (2R,3S)-(53) is obtained. In both cases the source of chirality is (+)-(R)-BINOL. The reason for this behaviour is poorly understood; the authors invoke two catalytic sites each of which leads to one of the enantiomeric products. One such site is thought to be blocked by competitive binding of the diketone (57).The same group also report the transformation (52) -+ (53) using a ‘chiral scandium triflate’ ~atalyst.~~.~~ Yamamoto and Ishihara have shown that the binaphthyl boron complex (59) a so-called Brsnsted acid-assisted Lewis acid (BLA) is an excellent catalyst for asymmetric Diels-Alder reactions [(a-bromoacrolein -+ (%)I.*’ The key feature in 74 H.Nishiyama Y. Itoh H. Matsumoto S.-B. Park and K. Itoh J. Am. Chem. Soc. 1994 116 2223. 75 S. Kanemasa S. Hamura E. Hatada and H. Yamamoto Tetrahedron Lett. 1994 35 7985. 76 K. Takai T. Kakiuchi and K. Utimoto J. Org. Chem. 1994 59 2671. 77 S. Kobayashi and H. Ishitani J. Am. Chem. Soc. 1994 116 4083. 78 S. Kobayashi M. Araki and I. Hachiya J. Org. Chem. 1994 59 3758. 79 S. Kobayashi H. Ishitani M. Araki and I. Hachiya Tetrahedron Lett. 1994 35 6325. K. Ishihara and H. Yamamoto J. Am. Chem. Soc. 1994 116 1561. Synthetic Methods 299 Ph -OH *i (48). 1.1 eq. ii Zn(CH21)p 2.2eq.PhvOH (4 (47) gayo,93% e.e. 81% 94% e.e. Scheme 10 this new type of catalyst is the presence of an appropriately positioned arylhydroxy group. Similar BLA catalysts have additionally been used to promote asymmetric aza-Diels-Alder and aldol-type reactions of imines.8 As well as being good catalysts of the Diels-Alder reaction lanthanide complexes have been used to effect many other reactions this year. Lanthanide(II1) tri- fluoromethanesulfonates are excellent catalysts for the anti aminolysis of epoxidess2 and the allylation of aldehydes with allyltrib~tylstannane.~~ A related catalyst scandium(I1)trifluoromethanesulfonate is an excellent catalyst for the Friedel-Crafts acylation of arene~.~~ The lanthanum-(S)-BINOL derived from lanthanum(1n) isopropoxide and (S)-BINOL complex is capable of effecting catalytic asymmetric efficient Michael reaction^.'^ Finally the synthesis of a ketone by addition of an organometallic reagent with carboxylate ion has seen dramatic improvement.Cohen and Ahn have shown that the K. Ishihara M. Miyata K. Hattori T. Tada and H. Yamamoto J. Am. Chem. SOC. 1994 116 10520. M. Chini P. Crotti L. Favero F. Macchia and M. Pineschi Tetrahedron Lett. 1994 35 433. 83 H. C. Aspinall A. F. Browning N. Greeves and P. Ravenscroft Tetrahedron Lett. 1994 35 4639. 84 A. Kawada S. Mitamura and S. Kobayashi SYNLETT 1994 545. 85 H. Sasai T. Arai and M. Shibasaki J. Am. Chem. SOC. 1994 116 1571. N. J. Lawrence 77 %. end0:exo 89:11,93% 8.8 (endo) oydopentadfene &CHO (59)(10 ml%) Br (58) >99% 99% 8.8.>99:1,exo mdo (59) Scheme 11 reaction of organolithium reagents with lithium carboxylates to produce ketones can be greatly improved by addition of cerium trichloride.86 Alkene Synthesis.-An excellent review of the mechanism of the Wittig reaction has appeared this year.87 Many new Wittig syntheses have been described this year including ones that are asymmetric in a chiral sense. The chiral Horner-Wad- sworth-Emmons (HWE) phosphonate (60) has been used to effect the kinetic resolution of the acrolein dimer (61). The reaction is 2 selective as expected for this type of trifluoroethoxy phosphonate and both geometric isomers are isolated in 86 Y. Ahn and T. Cohen Tetrahedron Lett.1994 35 203. " E. Vedjes and M. J. Peterson Top. Stereochem. 1994 21 1. Synthetic Methods KN(SiMe& 00 [i8]crown-6 (R’),dJLO,R -(60)R’ = CFSCH20 14 % 94% e.e. 81% 98% e.e. fl (62)R’ = CH,O (61) with (60) Scheme 12 excellent diastereoisomeric purity (Scheme 12a).88 Similar chiral HWE reagents have also been used to resolve ( & )-2-phenylpropanal; the best trans selectivity is obtained with R = methoxy as with (62) (d.e. 60O/0).*~ Denmark and Rivera have used the phosphonate (63) in a similar fashion.” The trans selectivity of some simple achiral Wittig reactions may be improved by concurrent daylight lamp irradiation in the presence of catalytic diphenyldisulfide.” Another Wittig protocol the McKelvie-Corey-Fuchs procedure (using PPhJCBr,) -for the synthesis of 1,l-dibromoalkenes from aldehydes -has been improved by the simple addition of triethylamine which is thought to destroy any dibromotriphenyl- phosphorane formed as a by-product .92 1,2-0xaphosphetanes (65) intermediates in the Horner-Wadsworth-Emmons reaction can be prepared ingeniously by intra- molecular dehydration of p-hydroxyalkylphosphonic acid monoesters (64) (Scheme 12b).93 Although the treatment of phosphonic acid with DCC results in syn stereospecific elimination of the oxaphosphetane (65),the reaction is presently limited since (64) is synthesized as a diastereoisomeric mixture (erythro:threo 2 1).Other named alkene syntheses have been improved and further developed this year. Andersson has shown that contrary to earlier reports the standard McMurry coupling of acetophenone using TiCl,(DME) .,/Zn-Cu actually gives (2)-2,3-diphenylb~t-2-ene.’~ Chan et a!.report a useful alternative to the Meyers’ modification 88 T.Rein N. Kann R. Kreuder B. Gangloff and 0.Reiser Angew. Chem. Int. Ed. Engl. 1994 33 556. 89 T. Furuta and M. Iwamura J. Chem. SOC.,Chem. Commun. 1994 2167. 90 S.E. Denmark and I. Rivera J. Org. Chem. 1994 59 6887. 91 J.K. Matikainen S. Kaltia and T. Hase SYNLETT 1994 817. 92 D. Grandjean P. Pale and J. Chuche Tetrahedron Lert. 1994 35 3529. 93 T. Kawashima M. Nakamura A. Nakajo and N. Inamoto Chern. Lett. 1994 1483. 94 P.G. Andersson Tetrahedron Lett. 1994 35 2609. 302 N. J. Lawrence (a) (6-r) 90%. Z:E95 5 [R~l "0- Scheme 13 of the Ramberg-Backlund reaction (KOH/CC~,/BU'OH);~~ using CBr,F, a milder positive bromine source carbene products are supressed resulting in cleaner reactions as in (66) -+ (67) (Scheme 13a).Another widely used alkene synthesis the Julia elimination has also seen modification. Fukumoto and coworkersg6 have found that SmIJHMPA usefully replaced the conventional reductant (Na/Hg). A useful alterna- tive to the Lindlar reaction has been reported by Fry and coworkers. They have used silica-gel-immobilized hydrosilane (SiHCl + silica) and Pd(PPh,) as an efficient system for the reduction of alkynes to Z alkene~.~' Finally two as yet unnamed alkene syntheses that use dimethylsulfonium methylide have been disclosed. Epoxides are converted into allylic alcohols (68) -+ (69),98while alkylhalides give terminal alkenes (70) -+(71),99 with the reagent.Both reactions involve elimination of dimethylsulfide from an intermediate sulfonium salt (Scheme 13b). Radical-based Methods.-An excellent review covering the use of transition metal promoted carbon-carbon bond forming reactions involving radicals has appeared this year.'" Ryu and Sonoda have developed an efficient procedure for the remote carbonylation of alcohols thereby producing b-lactones. lo' The process (72) -+ (73) 95 T.-L. Chan S. Fong Y. Li T.-0. Man and C.-D. Poon J. Chem. SOC.,Chem. Commun. 1994 1771. 96 M. Ihara S. Suzuki T. Taniguchi Y. Tokunaga and K. Fukumoto SYNLETT 1994 859. '' A. D. Kini D.V. Nadkarni and J. L. Fry Tetrahedron Lett.1994 35 1507. 98 L. Alcaraz J. J. Harnett C. Mioskowski J. P. Martel T. Le Gall D.-S. Shin and J. R. Falck Tetrahedron Lett. 1994 35 5449. 99 L. Alcaraz J. J. Harnett C. Mioskowski J. P. .Martel T. Le Gall D.-S. Shin and J. R. Falck Tetrahedron Lett. 1994 35 5453. 100 J. Iqbal B. Bhatia and N. K. Nayyar Chem. Rev. 1994,94 519. S. Tsunoi I. Ryu and N. Sonoda J. Am. Chem. SOC. 1994 116 5473. Synthetic Methods (74) (73) Scheme 14 facilitated by lead tetraacetate involves generation of an 0-centred radical (74) followed by 1,5-H transfer to create a new radical (75) which is trapped with carbon monoxide. Oxidation of the resulting radical (76) generates the 6-lactone (73) (Scheme 14). Crich and coworkers have developed a new method for the generation of acyl radicals.Treatment of acyl chlorides with sodium phenyltelluride gives an intermediate acyl telluride that decomposes to the acyl radical.lo2 Cossy et al. have described a new and very efficient method for the generation of alkyl radicals by irradiation of alkyl chlorides (at 254 nm) in the presence of triethylami~~e."~ Jones and coworkers have shown that the combination of cobalt(I1) chloride and a Grignard reagent is capable of generating aryl radicals. The protocol is an alternative to tin hydride in aryl radical cyclizations as demonstrated by the conversion of the amide (77) into the indol-2(3H)- one (78) (Scheme 15a).lo4 A novel radical cyclization of alkyl azides has been described by Kim et al.lo5 The intramolecular addition of any alkyl radical to an azide (79) -,(80) provides an efficient route to N-heterocycles (Scheme 15b).3 Reduction Much effort has been spent on the development of new reagents for the selective reduction of carbonyl compounds and their derivatives especially ketones. O6 Established asymmetric protocols using oxazaborolidine catalysts have seen wide- spread use for the borane reduction of ketones [(Sl) + (82)] (Scheme 16a). New oxazaborolidine catalysts introduced this year include the indene-derived (83).' O7 The B-hydroxysulfoximine (86) acts as a good catalyst for the enantioselective reduction of ketimine derivatives e.g. (84) - (85).'08 The same catalyst has also been used to effect lo' D. Crich C. Chen J.-T. Hwang H.W. Yuan A. Papadatos,and R. I. Walter J. Am. Chem.SOC.,1994,116 8937. lo3 J. Cossy J.-L. Ranaivosata and V. Bellosta Tetrahedron Lett. 1994 35 8161. lo4 A. J. Clark D. I. Davies K. Jones and C. Millbanks J. Chem. SOC. Chem. Commun. 1994 41. lo' S. Kim G. H. Joe and J.Y. Do J. Am. Chem. SOC. 1994 116 5521. lo6 M. Wills and J.R. Studley Chem. Ind. 1994 552. lo' Y. Hong Y. Gao X. Y. Nie and C. M. Zepp Tetrahedron Lett. 1994 35 6631. lo' C. Bolm and M. Felder SYNLETT 1994 655. 304 N. J. Lawrence I AIBN Bu3SnH 1wN3 -Q I pTolSO;1cI '' (80) (b) (79) 88% Scheme 15 HN OH Ph-:+A4 Ph 0- Ph (S),64%. 70% 8.8. (86) Scheme 16 the enantioselective reduction of ketones with sodium borohydride and chloro- trimethylsilane (Scheme 16b).Io9 Amines (89) are obtained in very high enantiomeric purity by the asymmetric hydrogenation of enamines (88) using the Buchwald catalyst (90).The active catalyst is generated by addition of two equivalents of n-butyllithium and 2.5 equivalents of phenylsilane to the titanium complex (90). Most importantly the hydrogenation is carried out under mild conditions; at room temperature and under 1atm of hydrogen (Scheme 17a)."' The system can also be used to effect the kinetic resolution of chiral enamines." Buchwald has additionally used the titanocene complex (90) to effect asymmetric hydrosilylation of ketones e.g. (91) + (92) (Scheme 17b).lI2 The complex is again activated by addition of Bu"Li and promotes the enantioselective transfer of hydrogen from polymethylhydrosiloxane (PMHS) to prochiral ketones.Other less lo9 C. Bolm A. Seger and M. Felder Tetrahedron Lett. 1994 35 8079. 'lo N. E. Lee and S.L. Buchwald J. Am. Chem. SOC. 1994 116 5985. A. Viso N. E. Lee and S. L. Buchwald J. Am. Chem. SOC.,1994 116,9373. '12 M. B. Carter B. SchiMMMtt A. Gutierrez and S. L. Buchwald J. Am. Chem. SOC. 1994 116 11 667. Synthetic Methods (90) R= (R,R)-1,l'-binaphth 2,Z-dolate (92). W%,95%e.e. Scheme 17 effective titanocene complexes have been used in a similar fashion by Halterman et u1.113 Other reagents used to obtain moderate enantioselectivity in the reduction of ketones include sodium borohydride supported on a polymer bearing chiral quater- nary ammonium groups;"4 sodium borohydride modified with carbohydrate deriva- tives;' l5 lithium aluminium hydride modified with ligands derived from (R)-myrtenol' l6 and P-pinene;' ' and chirally modified Pt/Al,03 for catalytic hydrogena- tion.' ' Several reagents have been designed for the achiral reduction of carbonyl compounds.Zirconium borohydride supported on a pyridine polymer is a useful reagent for the reduction of aldehydes and ketones; unlike zirconium borohydride the supported reagent is stable.' Polymethylhydrosiloxane (PMHS) a cheap industrial polymeric silane efficiently reduces esters and carboxylic acids in the presence of titanium',' and zirconium alkoxides. Ketones have also been reduced by tributyltin hydride in the presence of silica ge1.'22.'23 Catalytic quantities of transition metal alkoxides such as Ti(O'Pr) have been found to accelerate the rate of reduction of ketones with catecholborane or BH,-THF dramatically.Experiments suggest catalysis is achieved by the formation of alkoxyborohydrides.' 24 'I3 R. L. Halterman T. M. Ramsey and Z. L. Chen J. Org. Chem. 1994 59 2642. 'I4 K. Adjidjonou and C. Caze Eur. Polym. J. 1994 30,395. 'I5 L. Sharma and S. Singh Ind. J. Chem Sec. B 1994 33 1183. T. J. Lu and S. W. Liu J. Chin. Chem. Soc. 1994 41 205. 'I7 T. J. Lu and S. W. Liu J. Chin. Chem. SOC. 1994 41 467. ''' G.Z. Wang T. Heinz A. Pfaltz B. Minder T. Mallat and A. Baiker,J.Chem. SOC. Chem. Commun. 1994 2047. 'I9 B. Tamani and N. Goudarzian J. Chem. Sac. Chem. Commun. 1994 1079. K. J. Barr S.C. Berk and S.L. Buchwald J. Org. Chem. 1994 59,4323. '" S. W. Breeden and N.J. Lawrence SYNLETT 1994 833. ''' B. Figadere C. Chaboche X. Franck J.-F. Peyrat and A. Cave J. Org. Chem. 1994 59 7138. V. T. Tam,C. Chaboche B. Figadere B. Chappe B. C. Hieu and A. Cave Tetrahedron Lett. 1994,35,883. C. W. Lindsley and M. DiMare Tetrahedron Lett. 1994 35 5141. 306 N. J. Lawrence Singaram and coworkers have continued their study of the highly effective aminoborohydride reducing agents. The species LiR,N-BH have been used to reduce chiral imines '25 and alkylcyclohexanones the latter with exceptionally high equatorial selectivity.'26 A new reagent described by the group a 1 1 lithium aluminium hydride-N-methylpyrrolidine complex is also a powerful reducing agent.Its reducing properties are comparable to LiAlH, but in contrast it is air and heat ~tab1e.l~~ A detailed study of the conjugate reduction of a$-enals and a,P-enones has appeared.'28 Selective 1,4-hydrogenation of a,fi-unsaturated aldehydes and ketones is effected by SC-1 nickel boride prepared from nickel chloride and sodium borohydr- ide.lZ9 A mixture of LiBH (cat.) and borane selectively reduces the carbonyl group of conjugated and unconjugated alkenones.' 30 Titanium(1v) isopropoxide/sodium borohydride' 31 and zinc b~rohydride'~~ have been developed as mild and efficient one-pot reducing systems for the reductive amination of formaldehyde. Alkyl aryl and aroyl azides are reduced efficiently to alkyl amines aryl amines and aryl amides respectively with sodium borohydride/copper(II) sulfate.' 33 Sulfoxides are reduced to sulfides by a variety of reagents including magnesium in methanol and catalytic mercury(I1) chloride;' 34 silica chloride;' 35 lithium aluminium hydride/titanium(Iv) chloride;' 36 and lithium/naphthalene (cat.)/PhCHO.'37 Sul-fones are photochemically reduced to sulfoxides using titanium dioxide as an efficient photocatalyst.' 38 N-Boc protected y-lactams are chemoselectively reduced to pyr- rolidines in the presence of esters nitriles carbamates and alkenes by lithium triethylborohydride followed by triethylsilane/boron trifluoride etherate.'39 Ultra- sound has been found to accelerate the aluminium amalgam reduction of 1,2-nitroalcohols to the corresponding aminoalcohol.' 40 Secondary cyclic allylic acetates are selectively deoxygenated to alkenes without rearrangement by lithium perchlor- ate promoted triethylsilane reduction.14' 4 Oxidation The development of the Sharpless asymmetric dihydroxylation (AD) methodology (93) -+ (94) has continued this year (Scheme 18). Many new ligands have been comparative data from the Sharpless group suggests that the phthalazine ligand class is currently the Detailed pictures of the reaction mechanism are 12' J. Harrison J. C. Fuller C.T. Goralski and B. Singaram Tetrahedron Lett. 1994 35 5201. 126 J. C. Fuller C. M. Belisle C. T. Goralski and 8. Singaram Tetrahedron Letr. 1994 35 5389. 12' J.C. Fuller E.L. Stangeland T.C. Jackson and B. Singaram Tetrahedron Lett. 1994 35 1515. M. Yamashita Y.Tanaka A. Arita and M. Nishida J. Org. Chem. 1994 59 3500. 129 C. M. Belisle Y. M. Young and B. Singaram Tetrahedron Lett. 1994 35 5595. A. Arase M. Hoshi T. Yamaki and H. Nakanishi J. Chem. Soc. Chem. Commun. 1994 855. 13' S. Bhattacharyya Tetrahedron Lett. 1994 35 2401. S. Bhattacharyya A. Chatterjee and S. K. Duttachowdhury J. Chem. SOC. Perking Trans. 1 1994 1. "' H.S. P. Rao and P. Siva Synth. Commun. 1994 24 549. "'G.H. Lee E.B. Choi E. Lee and C.S. Pak Tetrahedron Lett. 1994 35 2195. F. Mohanazadeh A. R. Momeni and Y. Ranjbar Tetrahedron Lett. 1994 35 6127. E. Akgiin K. Mahmood and C.A. Mathis J. Chem. SOC. Chem. Commun. 1994 761. D. Guijarro and M. Yus Tetrahedron Lett. 1994 35 2965. 13' N. Somasundaram K. Pitchumani and C. Srinivasan J. Chem.SOC.,Chem. Commun. 1994 1473. C. Pedregal J. Ezquerra A. Escribano M. C. Carreiio and J. L. G. Ruano Tetrahedron Lett. 1994,35 205 3. 140 R. W. Fitch and F. A. Luzzio Tetrahedron Lett. 1994 35 6013. D. J. Wustrow W. J. Smith 111 and L.D. Wise Tetrahedron Lett. 1994 35 61. E. J. Corey M.C. Noe and M. J. Grogan Tetrahedron Lett. 1994 35 6427. 14' G.A. Crispino A. Makita Z.-M. Wang and K. B. Sharpless Tetrahedron Lett. 1994 35 543. Synthetic Methods Me0 OMe (DHQD)zPHAL (93) (94) Scheme 18 Binding cleft; phthalazine ring as the floor and bystander rnethoxyquinoline unit as a Active dihydro- Me0 -Bystander quinidine ligand- dihydroquinidine ligand emerging from the Sharpless gro~p'~~,'~' and other^.'^^.'^' The high selectivity of the reaction is explained by the model (95) which possesses an enzyme-like binding pocket.The binding cleft is set up by the phthalazine ring as the floor and the bystander alkaloid quinoline group as a perpendicular wall. The alkene binds selectively in the pocket allowing controlled delivery of the osmium tetroxide by the active alkaloid quinuclidine group. The high enantioselectivity of the reaction has in a very short period of time led to numerous practical applications including preparations of the paclitaxel side the paclitaxel A ring;'49 a kilogram-scale preparation of enantiopure hydrobenzoin; ''O the chiral auxiliary trans-2-phenylcyclohexanol;''' the pheromone ( + )-disparlure;'52 the cytotoxic lactones goniobutenolides A and B;ls3 conduritol 144 H.C. Kolb P.G. Anderson and K. B. Sharpless,J. Am. Chem. Soc. 1994,116,1278; P.-0. Norrby H. C. Kolb and K. B. Sharpless J. Am. Chem. Soc. 1994 116 8470; P.-0. Norrby H.C. Kolb and K. B. Sharpless Organometallics 1994 13 344. 145 H. Becker P. T. Ho H.C. Kolb S. Loren P.-0.Norrby and K. B. Sharpless Tetrahedron Lett. 1994,35 7315. E. J. Corey M.C. .Noe and S. Sarshar Tetrahedron Lett. 1994 35 2861. 14' B. B. Lohray V. Bhushan and E. Nandanan Tetrahedron Lett. 1994,35 4209. 14* Z.-M. Wang H.C. Kolb and K. B. Sharpless J. Org. Chem. 1994 59 5104. 149 T. Nakamura N. Waizumi Y. Horiguchi and I. Kuwajima Tetrahedron Lett. 1994 35 7813. Z.-M. Wang and K. B. Sharpless J. Org. Chem. 1994 59 8302 Is' S. B. King and K. B. Sharpless Tetrahedron Lett.1994 35 561 1. S.Y. KO Tetrahedron Lett. 1994 35 3601. Is' D. Xu and K. B. Sharpless Tetrahedron Lett. 1994 35 4685. 308 N. J. Lawrence E;'54 the C-4 building-block ( -)-diep~xybutane;'~~ a Mosher's acid precurs~r;'~~ the anticancer agent camptothecin;' 57 and intermediates for oxindole alkaloid,' 58 carbohydrate,' 59 and prostaglandin' 6o synthesis. Many alkene derivatives have been the topic of methodical study including cis allylic alcohols;'61 cyclic cis alkenes;'62 and a-and p-farne~ene'~~ derivatives. In addition the AD procedure has and gerani01'~~ been shown to be tolerant of sulfides disulfides and 1,3-dithiane f~nctionality.'~~ Two heterogeneous systems for asymmetric dihydroxylation have been developed; poly- meric supports containing quinine 4-chlorobenzoate derivatives'66 and (bisdihyd- roquinidy1)pyridazine ligand~'~~ assist the asymmetric dihydroxylation of alkenes to the same degree as do the free alkaloids.Epoxidation continues to draw much attention. The Jacobsen catalyst (97) has been the centre of most asymmetric methods. It has been used to effect the highly enantioselective catalytic epoxidation of trisubstituted olefins.'68 However this [Mn(salen)]-catalysed reaction has proved ineffective for the epoxidation of trans-disubstituted olefins. Jacobsen and coworkers have indirectly solved this problem by showing that trans epoxides can be obtained by the epoxidation of cis-disubstituted alkenes. The generation of both cis and trans epoxides from the reaction of cis alkenes is a feature of the [Mn(salen)]-catalysed reaction (Scheme 19a).Jacobsen has now found that chiral quaternary ammonium salt (96) greatly assists the formation of the trans epoxide (Scheme 19b).'69 In this way cis-stilbene gives the trans epoxide in the presence of (97) [for comparison trans stilbene undergoes epoxidation with (98) with 27% e.e.1. Jacobsen and his group have also developed a protocol for the enantioselective epoxidation of styrene -a subtrate that normally gives only 5&70% e.e. at best. They found the epoxidation can be carried out at low temperature (-78°C) under homogeneous conditions in dichloromethane using the [Mn(salen)]-catalyst (99) using rn-CPBA as the terminal oxidant thereby obtaining 86% e.e.I7O The increase in selectivity is thought to be a consequence of a combination of better facial selectivity and also a suppression of step 2 in Scheme 19a.Among other examples of the [Mn(salen)]-catalysed reactions are procedures described by the groups of Kat- s~ki,'~','~~ Mohajer,17' and Pietikainen.'76 M~kaiyama,'~~.'~~ 154 S. Takano T. Yoshimitsu and K. Ogasawara J. Org. Chem. 1994 59 54. 155 K. P. M. Vanhessche Z.-M. Wang and K. B. Sharpless Tetrahedron Lett. 1994 35 3469. Y. L. Bennani K. P. M. Vanhessche and K. B. Sharpless Tetrahedron Asymmetry 1994 5 1473. 157 F.G. Fang S. P. Xie and M. W. Lowery J. Org. Chem. 1994 59 6142. A. C. Peterson and J. M. Cook Tetrahedron Lett. 1994 35 2651. I. Henderson K. B. Sharpless and C.-H. Wong J. Am.Chem. SOC. 1994 116 558. 160 S. Takano T. Yoshimoto and K. Ogasawara SYNLETT 1994 119. 161 M. S. Van Nieuwenhze and K. B. Sharpless Tetrahedron Lett. 1994 35 843. Z.-M. Wang K. Kakiuchi and K. B. Sharpless J. Org. Chem. 1994 59 6895. M.A. Brimble D. D. Rowan and J.A. Spicer Tetrahedron Lett. 1994 35 9445. D. Xu C.Y. Park and K.B. Sharpless Tetrahedron Lett. 1994 35 2495. 165 P. J. Walsh P.T. Ho S. B. King and K. B. Sharpless Tetrahedron Lett. 1994 35 5129. 166 D. Pini A. Petri and P. Salvadori Tetrahedron 1994 50 11 321. 167 B. B. Lohray E. Nandanan and V. Bhushan Tetrahedron Lett. 1994 35 6559. B. D. Brandes and E.N. Jacobsen J. Org. Chem. 1994 59 4378. 169 S. B. Chang J. M. Galvin and E.N. Jacobsen J. Am. Chem. SOC.,1994 116 6937.I7O M. Palucki P.J. Pospisil W. Zhang and E.N. Jacobsen J. Am. Chem. SOC. 1994 116 9333. 171 R. hie N. Hosoya and T. Katsuki Chem. Lett. 1994 255. H. Sasaki R. Irie T. Hamada K. Suzuki and T. Katsuki Tetrahedron 1994 50 11 827. 173 K. Imagawa T. Nagata T. Yamada and T. Mukaiyama Chem. Lett. 1994 527. 174 T. Nagata K. Imagawa T. Yamada and T. Mukaiyama Chem. Lett. 1994 1259. D. Mohajer and S. Tangestaninejad Tetrahedron Lett. 1994 35 945. 176 P. Pietikainen Tetrahedron Lett. 1994 35 941. Synthetic Methods 0 R/" -step 2 R' Ph a-(97) 4 md9 C Ph? (96)25 dsC NaOCl Ph Ph 90%e.e. mns:cis>96:4 Scheme 19 The direct epoxidation of simple alkenes with hydrogen peroxide may be achieved by in situ activation of the oxidant with diphenylphosphinic anhydride and other organophosphorus electrophiles.' 77 The active epoxidizing agent is thought to be diphenylperphosphinic acid.Other agents used to effect epoxidation of alkenes include manganese(u1) meso-tetraphenylporphyrin,Bu:NIO and imidazole;' 78 zeolite beta (Ti-Al-P) with t-butylhydroper~xide;'~~ [Ru0,(bipy)(10,(0H),)1.1.5H20 and NaIO,;' 8o and manganese-containing polyoxometalates so-called 'inorganic por- phyrins' e.g. WZnMn2((ZnW),,),.'81 The synthesis of epoxides from sulfur ylides and aldehydes has been known for some time. Aggarwal et al. have developed an ingenious reagent system that uses catalytic sulfide.''' A mixture of aldehyde diazo compound catalytic dimethyl sulfide and rhodium acetate provides an efficient route to epoxides (100)+(101) with trans selectivity.The sulfur ylide is generated from the rhodium-catalysed reaction of the 177 A. S. Kende P. Delair and B. E. Blass Tetrahedron Lett. 1994 35 8123. D. Mohajer and S. Tangestaninejad Tetrahedron Lett. 1994 35 945. 179 T. Sato J. Dakka and R.A. Sheldon J. Chem. SOC., Chem. Commun. 1994 1887. A. J. Bailey W. P. Griffith A. J. P. White and D.J. Williams J. Chem. SOC.,Chem. Commun. 1994 1833. R. Neumann and M. Gara J. Am. Chem. SOC. 1994 116 5509. V. K. Aggarwa1,H. Abdel-Rahman R. V. H. Jones H. Y. Lee,and B. D. Reid,J. Am. Chem. SOC.,1994,116 5973. N. J. Lawrence Scheme 20 sulfide ahd diazo compound. The ylide reacts with the aldehyde to provide the epoxide and return the sulfide to the catalytic cycle (Scheme 20).The oxidation of alcohols has been well studied this year. Alcohols are transformed into aldehydes and ketones with a variety of new reagents including CrO on wet al~rnina,"~ magnesium chlorochromate,'84 o-iodoxybenzoic acid,'85 ButOOH/CuC1 (~at.)/Bu,NBr,"~ and Mn02/Ru(1r) (cat.) for the oxidation of non-activated secondary alcohols.187 The aerobic oxidation of alcohols can be achieved with a ruthenium(1v) porphyrin complex;"' a triple catalytic system involving a ruthenium complex a cobalt complex and a benzoq~inone;"~ and cobalt(r1) Schiff bases with 2-methylpropanal. 190 Another clean way to oxidize alcohols has been developed by Muzart et al. They used sodium percarbonate (Na2C03.1 .5H202)with catalytic PDC and Adogen 464TM as a phase-transfer catalyst to effect the conversion of allylic and benzylic alcohols into their carbonyl counterpart^."^ Dimethyldioxirane has been used to oxidize a- methylbenzylalcohols to their corresponding ketones in excellent yield.192 1,2-Diols are oxidized to 1 ,Zdiketones with 4-acetamido-TEMPO in the presence of TsOH.'~~ Meyer and Schreiber have made important observations regarding the Dess-Martin oxidant.They found that the rate of oxidation of secondary alcohols is considerably enhanced if water is added to the reaction medium.'94 The use of TPAP (tetra-n-propylammonium perruthenate) has been reviewed.195 Secondary amines bearing an a-proton are efficiently oxidized by TPAP (cat.) and NMNO to imine~;'~~ similarly hydroxylamines are converted into nitrones.lg7 Molecular oxygen has been used as the terminal oxidant in the Baeyer-Villager reaction of ketones to lactones in the presence of benzaldehyde -as coreductant -in the lE3 M. Hirano T. Kobayashi and T. Morimoto Synth. Commun. 1994 24 1823. '13' P. H. J. Carlsen and K. AasboMMM Synth. Commun. 1994 24 89. lS5 M. Frigerio and M. Santagostino Tetrahedron Lett. 1994,35 8019. lS6 L. Feldberg and Y. Sasson J. Chem. SOC.,Chem. Commun. 1994 1807. lS7 U. Karlsson G.-Z. Wang and J.-E. Backvall J. Org. Chem. 1994 59 1196. lE8S.Y.S. Cheng N. Rajapakse S.J. Rettig and B. R. James J. Chem. SOC. Chem. Commun. 1994 2669. lE9 G.-Z. Wang U. Andreasson and J.-E. Backvall J. Chem. SOC.,Chem. Commun. 1994 1037. 190 S. J. S. Kalra J.Iqbal and T. Punniyamurthy Tetrahedron Lett. 1994,35 4847. 19' J. Muzart A. NAit Ajjou and S. Ait-Mohand Tetrahedron Lett. 1994 35 1989. 19' F. Kovac and A. L. Baumstark Tetrahedron Lett. 1994,35 8751. 19' M. G. Banwell V. S. Bridges J. R. Dupuche S. L. Richards and J. M. Walter J. Org. Chem. 1994 59 6338. 19' S. D. Meyer and S. L. Schreiber J. Org. Chem. 1994 59 7549. 19' S. V. Ley J. Norman,W. P. Griffith and S. P. Marsden Synthesis 1994 639. 19' A. Goti and M. Romani Tetrahedron Lett. 1994,35 6567. lg7 A. Goti F. De Sarlo and M. Romani Tetrahedron Lett. 1994 35 6571. Synthetic Methods o=Bu'cHo* bm(104) (0.01 eq.) 47% 69% 8.8 (la), R = Bu' Scheme 21 absence of metal catalysts and in chlorohydrocarbon solvents.198 Hydrotalcite catalysts have also provided a heterogeneous Baeyer-Villager oxidant in combination with molecular oxygen and an a1deh~de.I~~ Bolm et al.have developed an asymmetric version of this process -the first non-enzyme asymmetric Baeyer-Villager reaction -using the copper complex (104); kinetic resolution of the ketone (+_)-(102) occurs with high stereoselectivity to give the lactone (103) and (S)-(102) (Scheme 21a).,0° The Baeyer-Villager-like oxidation of or-alkoxy cyclic ketones is effected by the nickel(I1) complex (107) by combined use of molecular oxygen and aldehydes.201 The process represents a good method for the synthesis of acetal carboxylic acids e.g. (105)-+ (106) (Scheme 21b). Rozen has used his powerful oxygen transfer agent the HOFaMeCN complex to oxidize thiophenes to their S,S-dioxides202 and sulfides to sulf~nes.~~~ The process is claimed to be non-polluting since the by-product is HF which can be scrubbed with Ca(OH) to give CaF,.The complex has also been used to oxidize or-amino acids to a-nitro acids.204 The same transformation of sulfides to sulfoxides can also be effected 19* K. Kaneda S. Ueno T. Imanaka E. Shimotsuma Y. Nishiyama and Y. Ishii J. Org. Chem. 1994,59 2915. 199 K. Kaneda S. Ueno and T. Imanaka J. Chem. SOC.,Chem. Commun. 1994 797. '0° C. Bolm G. Schlingloff and K. Weickhardt Angew. Chem. Int. Ed. Engl. 1994,33 1848. '01 E. Hata T. Takai T. Yamada and T. Mukaiyama Chem. Lett. 1994 535. '02 S. Rozen and E. Bareket J. Chem. SOC.,Chem. Commun. 1994 1959. '03 S.Rozen and Y. Bareket Tetrahedron Lett. 1994 35 2099. 204 S. Rozen A. Bar-Haim and E. Mishani J. Org. Chem. 1994 59 1208. N. J. Lawrence HS)-H pF6-Phi0 (1 a&) Me0 (109) 76% 63% 8.8 Scheme 22 cleanly with ruthenium(II1) chloride(cat.)/sodium periodate205 and oxonem in aq. acetone (pH 7.5-8.0).206 Katsuki and coworkers have used the manganese salen catalyst (110) to effect the asymmetric oxidation of sulfides (108) -+(109) (Scheme 22a).207 Other reagents that effect the transformation of sulfides into sulfoxides include hydrogen peroxide in the presence of imines (cat.) (moderate enantioselectivity is observed with enantiomerically pure imines);208 hydrogen peroxide/metiiyltrioxo- rhenium(v~~)(cat.).~~~ Oxidation of sulfides can also be achieved via sulfonic acid catalysed oxygen transfer from selenoxides.210 The efficient functionalization of alkanes via oxidation of remote C-H bonds remains one of the great challenges in organic chemistry.The oxidation of weakly activated C-H bonds has recently been reviewed." Such oxidations using ruthenium trichloride and peracids2I2 have been explored this year. Resnati and coworkers" 205 W. Su Tetrahedron Lett. 1994 35 4955. 206 K. S. Webb Tetrahedron Lett. 1994 35 3457. 207 K. Noda N. Hosoya K. Yanai R. hie and T. Katsuki Tetrahedron Lett. 1994 35 1887. 208 P. C. Bulman Page J. P. Heer D. Bethell E. W. Collington and D. M. Andrews Tetrahedron Lett. 1994 35 9629. *09 W. Adam C. M. Mitchell and C. R. Saha-Moller Tetrahedron 1994 50 13 121.210 D.J. Procter S. .J. Lovell and C. M. Rayner SYNLETT 1994 204. 211 0.Reiser Angew. Chem. Int. Ed. Engl. 1994 33 69. 212 S.4. Murahashi Y. Oda N. Komiya and T. Naota Tetrahedron Lett. 1994 35 7953. 213 A. Arnone M. Cavicchioli V. Montarni and G. Resnati J. Org. Chem. 1994 59 5511. Synthetic Met hods 0 Scheme 23 have used the Desmarteau perfluorodialkyloxaziridine (1 13) to hydroxylate the C-5 atom of 5P-steroidal systems selectively e.g. (1 11) + (1 12) (Scheme 22b). Hay and coworkers have found that biphenol(ll4) catalyses the oxidation of diarylmethanes to benzophenones by molecular oxygen in the presence of CuCl (Scheme 22c).214 Activated aryl methyl-groups have been oxidized to aldehydes in a two-step process. The substituted toluene (115) is first converted into the enamine (116) by treatment with DMF-acetal which is oxidized by uncatalysed periodate cleavage of the carbon-carbon double bond to give the aldehyde (1 17) (Scheme 23).21 Iqbal and coworkers have studied the oxidation of various substrates mediated by cobalt complexes.They have shown that 1,2-diaryl-1,2-diketonescan be obtained by the cobalt(I1)-catalysed autoxidative coupling of aromatic aldehydes in the presence of n-butanal in acetonitrile. Oxidation to the corresponding carboxylic acid occurs in the presence of acetic anhydride.216 The cobalt Schiff-base complex (118) is also an excellent catalyst for alcohol oxidation,2 l7 and allylic and benzylic oxidation in the presence of oxygen and 2-oxocyclopentanecarboxylate.2 Similarly pentafluoroben- zeneseleninic acid is an efficient reagent for the oxidation of alcohols and the allylic oxidation of alkene~.~~' (1 18) Weinreb and coworkers220 have developed an efficient method for the oxidation of amides by exploiting the transformation of o-aminobenzamides to or-methoxybenzam- ides.For example diazotization of (119) in the presence of a catalytic amount of copper(1) chloride in dry methanol affords the synthetically useful a-methoxyamide 'I4 G. Barbiero W.-G. Kim and A.S. Hay Tetrahedron Lett. 1994,35 5833. *Is M. G. Vetelino and J. W. Coe Tetrahedron Lett. 1994 35 219. 'I6 T. Punniyamurthy S.J. S. Kalra and J. Iqbal Tetrahedron Lett. 1994 35 2959. 'I7 T. Punniyamurthy and J. Iqbal Tetrahedron Lett.1994 35 4007. 'I8 T. Punniyamurthy and J. Iqbal Tetrahedron Lett. 1994 35 4003. '19 D. H. R. Barton and T.-L. Wang Tetrahedron Lett. 1994 35 5149. 220 G.H. Han M.C. McIntosh and S. M. Weinreb Tetrahedron Lett. 1994 35 5813. 314 N. J. Lawrence Q HNO, CuCl (cat.) MeO MeOH * Po Cyo (1 19) (120)69% Scheme 24 (120) (Scheme 24). The tra sformation is thought to proceed uiu copper@)-catalys d formation of an aryl radical from the diazonium salt of (1 19).This radical is now ideally placed to abstract the a-hydrogen of the piperidine ring to form the a-radical which is oxidized to an acyl iminium ion; this is captured by the alcohol to give the benzamide (120). 5 Protection The very important area of protecting group methodology has seen much study this year and the use of enzymes in protecting group chemistry has been reviewed.221 Alcohols.-Primary alcohols may be protected as 1,1,1,3,3,3-hexafluoro-2-phenyliso-propyl (HIP) ethers prepared via facile Mitsunobu condensation of HIP alcohol and DEAD and triphenylphosphine.The HIP ethers are remarkably stable to both acidic and basic conditions and to a wide range of oxidizing and reducing agents.222 The protecting group is easily removed by treatment with stoichiometric lithium naph- thalenide. Esters can be made using the novel triphenylphosphine sulfamide complex (121),which promotes the Mitsunobu-like coupling between alcohols and carboxylic or nitrogen a,co-Diols are selectively monoacylated in ester/octane solvent mixtures when catalysed by strongly acidic ion-exchange resins.224 Trityl-protected alcohols may be deprotected by C1 in chloroform.225 THP ethers of alcohols and phenols may be formed by the use of Spanish Sepiolite clay and 3,4-dih~dropyran.~~~ Majetich et a!.have found that methyl ethers a popular protecting group for phenols may be cleaved by L-Selectride@ and Super-Hydridem under reflux in THF.227 Brusee and coworkers have shown that another popular protecting group the silyl group may ’” H. Waldmann and D. Sebastian Chem. Rev. 1994,94 911. ”’ H.-S. Cho J.R. Yu and J.R. Falck J. Am. Chem. SOC. 1994 116 8354. 223 J. L. Castro V.G. Matassa and R. G. Ball J. Org. Chem. 1994 59 2289. 224 T. Nishiguchi S. Fujisaki Y. Ishii Y. Yano and A. Nishida J. Org. Chem. 1994 59 1191.”’ J. Fuentes T. Cuevas and M. A. Pradera Synth. Commun. 1994 24 2237. 226 J. M. Campelo A. Garcia F. Lafont D. Luna and J.M. Marinas Synth. Commun. 1994 24 1345. 227 G. Majetich Y. Zhang and K. Wheless Tetrahedron Lett. 1994 35 8727. Synthetic Methods 315 also be cleaved by a hydride reagent under special conditions. They found that t-butyldimethylsilyl ethers flanked by a carbon atom bearing an amine or hydroxyl group are selectively cleaved in the presence of isolated silyl ethers e.g. (122) + (123) (Scheme 25a) by lithium aluminium hydride.’” Silyl ethers can also be prepared by silylation of alcohols with sila~anes~~~ by the action of catalytic and hydro~ilanes~~~ TBAF. The regioselective protection of diols as monosilyl derivatives occurs by reaction of dibutylstannanediyl acetals which can themselves be made by a new method utilizing microwave heating technology,231 and a silyl chloride reagent.232 Allyl protected alcohols are rapidly deprotected by a two-step procedure involving allylic bromination (NBS) and sodium hydroxide work-~p.~~~ NBS has also been used to deprotect benzyl esters.234 Allyl protected phenols are deprotected with Pd(Ph3)4/NaBH4.235 The 1-adamantyloxycarbonyl group has been used as a novel protecting group for phenols bearing strongly electron-withdrawing Ley et al.have introduced cyclohexane- 1,2-diacetals as protecting groups for vicinal diols in carbohydrate^.^^' This procedure works especially well for manno-type sugars resulting in 3,4-diol protection as in (124) -+ (125) (Scheme 25b).Earlier work from the Ley group had shown that protection of trans 1,2-diols occurs with bisdihydropyran. However this reagent shows little preference between the 2,3 and 3,4-diol groups of various D-glucopyranose derivative^.'^' But only one dispiroketal derivative (1 27) is formed between the glucopyranose derivative (126) and the chiral bisdihydropyran (128) (Scheme 25c).239 When the enantiomeric bisdihydropyran is used only 2,3 protection is observed. Similar enantio- and regioselective protection was observed with myo-inositol derivative^.^^' Alcohols are converted quantitatively into their corresponding alkyl chlorides by treatment with chlorotrimethylsilane in the presence of bismuth(m) chloride (5m~l%).~~l The diphenylmethylsilylethyl (DPSE) group has been introduced as a versatile protecting group of P-OH groups for use in oligonucleotide ~ynthesis.~~~,~~~ Thiols are protected as phthalimidomethyl sulfides by reaction with bromomethyl- phthalimide (PimBr).244 Ketones and Aldehydes.-Dithioacetals may be prepared from dithiols and the carbonyl compound with anhydrous cobalt(i1) bromide dispersed on silica gel.245 On the other hand dithioacetals and ketals are readily deprotected photochemically using 228 E.F.J. de Vries J. Brussee and A. van der Gen J. Org. Chem. 1994 59 7133. 229 Y. Tanabe M. Murakami K. Kitaichi and Y. Yoshida Tetrahedron Lett. 1994 35 8409. 230 Y. Tanabe H. Okumura A. Maeda and M. Murakami Tetrahedron Lett. 1994 35 8413. 231 A.Morcuende S. Valverde and B. Herradon SYNLETT 1994 89. 232 D. A. Leigh R. P. Martin J. P. Smart and A.M. Truscello J. Chem. SOC.,Chem. Commun. 1994 1373. 233 R. R. Diaz C. R. Melgarejo M.T. P. Lopez-Espinosa and I. I. Cubero J. Org. Chem. 1994 59 7928. 234 M.S. Anson and J.G. Montana SYNLETT 1994 219. ’’’ R. Beugelmans S. Bourdet A. Bigot and J. P. Zhu Tetrahedron Lett. 1994 35 4349. 236 I. Niculescuduvaz and C. J. Springer J. Chem. Res. 1994 242. 237 S.V. Ley H. W. M. Priepke and S. L. Warriner Angew. Chem. Int. Ed. Engl. 1994 33 2290. 238 A. B. Hughes S.V. Ley H. W. M. Priepke and M. Woods Tetrahedron Lett. 1994 35 773. 239 D.A. Entwistle A. B. Hughes S.V. Ley and G. Visentin Tetrahedron Lett. 1994 35 777. 240 P. J. Edwards D. A. Entwistle C. Genicot K.S. Kim and S. V. Ley Tetrahedron Lett. 1994 35 7443. 241 M. Labrouillere C. Le Roux H. Gaspard-Iloughmane and J. Dubac SYNLETT 1994 723. 242 V.T. Ravikumar and D. L. Cole Gene 1994 149 157. 243 V. T. Ravikumar T. K. Wyrzykiewicz and D. L. Cole Tetrahedron 1994 50 9255. 244 Y.-D. Gong and N. Iwasawa Chem. Lett. 1994 2139. 245 H. K. Patney Tetrahedron Lett. 1994 35 5717. N. J. Lawrence OTBMDS 122 123 OMe JdoMe OH OM0 CSA I 124 OM0 125 Hi&+ CSA HoOMe 126 127 ph R=OTBDMS Scheme 25 tris(p-chloropheny1)pyrylium perchlorate as a sensitizer246 or with DDQ.247 Oxathioketals are deprotected by TMSOTf-catalysed oxathioacetal transfer to free248 or p~lymer-bound~~~ p-nitrobenzaldehyde. Similarly acetals and ketals may be deprotected with acetyl chloride and samarium(II1) chloride.250 Ketones and aldehydes may be protected as their 4-trimethylsilylmethyl-l,3-dioxolanederivatives thereby enabling mild fluoride ion assisted deprotection.2s Similarly p-methoxyphenylethyl- ene acetals act as protected aldehydes and ketones; oxidative deprotection is effected by DDQ.252 Aldehydes may be regenerated from enol ethers by treatment with the combined reagent Bu4NF-BF,.Et20; this procedure was designed to tolerate alkyltin f~nctionality.~ Carboxylic Acids.-Cossy et al.report the mild and neutral hydrolysis of prenyl esters using iodine in cy~lohexane.~~~ The complex AICl,.N,N-dimethylaniline has been shown to be a very mild reagent for the cleavage of methyl benzyl methoxymethyl methylthiomethyl methoxyethoxymethyl and (P-trimethylsily1)ethoxymethyl es-ter~.~~~ The 1-(4-methoxyphenyl)ethyl (MPE) group has been shown to be a good 246 M.Kamata Y. Murakami Y. Tamagawa M. Kato and E. Hasegawa Tetrahedron 1994 50 12821. 247 K. Tanemura H. Dohya M. Imamura T. Suzuki and T. Horaguchi Chem. Lett. 1994,965. 248 T. Ravindranathan S. P. Chavan J. P. Varghese S. W. Dantale and R. B. Tejwani J. Chem. SOC.,Chem. Commun. 1994 1937. 249 T. Ravindranathan S. P. Chavan and M. M. Awachat Tetrahedron Lett. 1994 35 8835. 250 S.-H. Wu and Z.-B. Ding Synth. Commun. 1994 24 2173. "' B. M. Lillie and M. A. Avery Tetrahedron Lett. 1994 35 969. 252 C. E. McDonald L. E. Nice and K. E. Kennedy Tetrahedron Lett. 1994 35 57. 253 V. Gevorgyan and Y.Yamamoto J. Chem. SOC. Chem. Commun. 1994 59. 254 J. Cossy A. Albouy M. Scheloske and D. G. Pardo Tetrahedron Lett. 1994 35 1539. 255 T. Akiyama H. Hirofuji A. Hirose and S. Ozaki Synth. Commun. 1994 24 2179. Synthetic Methods R2 &02< (131) '' and As)=. S Scheme 26 carboxyl protecting group. MPE esters are cleaved under mild conditions (1% TFA in CH2C12) without cleavage of t-butyl esters and Boc Magnesium in methanol also effects the cleavage of alkyl esters; the order of reactivity was found to be p-nitrobenzoate > acetate > benzoate > pivaloate 2 triflu~roacetamide.~~~ Car-boxylic acids may be protected as their 2-cyanoethyl esters which can be cleaved under mild conditions using TBAF in DMF/THF.258 Carboxylic esters are efficiently prepared from mixtures of the free acids and alcohols by the action of p-(tri- fluoromethy1)benzoic anhydride and TiC14/AgCI04 at.).^ 59 Acids are also trans- formed into esters by activation with NBS and triphenylphosphine.260 Symmetrical carboxylic acid anhydrides are prepared simply from the acid with triphosgene.261 Esterification with inversion of the alcohol centre (129) + (131)-a process similar to the Mitsonobu reaction-is possible by heating a carboxylic acid with the appropriate (S)-propargyl dithiocarbonate (129).The reaction is thought to take place by an SN2-type attack of the carboxylate anion upon the protonated betaine (130) [derived by sigmatropic rearrangement and cyclization of (129)] (Scheme 26).262 Amines.-Much effort has been concentrated on the development of selective methods for the removal of amine protecting groups.N-Boc protected amines are efficiently deprotected in the presence of t-butyl ester groups by dry HCl in ethyl acetate;263 the product hydrochloride salt often precipitates directly from the reaction mixture. Fmoc (N-Fluorenylmethoxycarbonyl) protected amines may be liberated by treatment with potassium fluoride in the presence of methyl ethyl t-butyl benzyl and p-methoxybenzyl ester~.~~~ N-Benzyl tertiary amines may be deprotected with ethyl chloroformate to give the corresponding debenzylated N-carbamate; the amine may be conventionally liberated finally by treatment with N,N-diethylaniline boron triiodide complex.265 N-Benzenesulfonamides or N-p-toluenesulfonamides are deprotected to the parent primary or secondary amine upon heating with excess samarium diiodide in THF/DM PU.66 256 M. S. Bernatowitz H.-G. Chao and G. Matsueda Tetrahedron Lett. 1994 35 1651. 257 Y.-C. Xu E. Lebeau and C. Walker Tetrahedron Lett. 1994 35 6207. 258 Y. Kita H. Maeda F. Takahashi S. Fukui T. Ogawa and K. Hatayama Chem. Pharm. Bull. 1994,42 147. 259 I. Shiina S. Miyoshi M. Miyashita and T. Mukaiyama Chem. Lett. 1994 515. 260 K. Sucheta G. S. R. Reddy D. Ravi and N. Rama Rao Tetrahedron Lett. 1994 35 4415. 261 R. Kocz J. Roestamadji and S. Mobashery J. Org. Chem. 1994 59 2913. 262 J. Boivin E. Hennet and S.Z. Zard J. Am. Chem. SOC. 1994 116 9739. 263 F. S. Gibson S.C. Bergmeier and H. Rapoport J.Org. Chem. 1994 59 3216. 264 J. Jiang W.-R. Li and M. M. Joullie Synth. Commun. 1994 24 187. 265 J.V. B. Kanth C.K. Reddy and M. Periasamy Synth. Commun. 1994 24 313. 266 E. Vedjes and S.Z. Lin J. Org. Chem. 1994 59 1602. 318 N. J. Lawrence Primary amines may be protected as their N,N-dimethylformamidine derivatives; the amine is regenerated by treatment with zinc(1r) Other protecting groups for amines include the 2,5-dimethylpyrrole group;268 the 2-adamantyl carbamate group for the protection of &-amino groups in peptide synthesis.269 Amide chemistry has seen much study this year. 2-Pentafluorothiophenyl esters have been shown to be useful acyl donors for amide bond formation.270 Amides are chemoselectively hydrolysed in the presence of esters by copper(~~)/glyoxal.~~ The N-(2-hydroxybenzyl) protecting group has been used for protection of the amide bond in solid-phase peptide synthesis overcoming problems with chain aggregation.272 Nitriles may be converted into amides by treatment with manganese dioxide on silica gel.273 N,N-Dialkyl carbamates -generated from the amine and carbon dioxide -are converted into the corresponding carbamoyl chloride with thionyl the carbon dioxide is effectively a phosgene replacement.6 Miscellaneous Preparations The accurate measurement of enantiopurity remains as important as ever. Burgess and Porte have introduced the optically pure boronic acid (132) as a new reagent for the determination of optical purities of 1,2 and 1,3-diols. In most cases the ‘H NMR signals of the methoxyl group of each diastereoisomeric boronic ester (133) show base-line resolution.275 The naphthyl acetic acid derivative (134),276,277 chlorofluoroacetic and the axially chiral benzoic acid (135)279 are reported to be reagents superior to Mosher’s acid for the chiral analysis of secondary alcohols (Scheme 27).If the optical purity of an alcohol requires enhancing then the method of Fleming and Ghosh can be used. They have shown that oxaloyl esters serve as useful intermediates for the improvement of the enantiomeric excess of chiral non-racemic alcohols; a sample of 1-naphthyl-1-ethanol of 92y0e.e. was raised to 99.6% in 78% yield by separation and hydolysis of the (R,R)+ (S,S) isomers from the meso (R,S) dias-tereoisomer of its oxaloyl diester.280 More drastic examples of the improvement of optical purity from 0 to 100% using a different principle have been described.The reaction used involves the deracemization of carbonyl compounds bearing an adjacent chiral centre. Vedjes et al. have shown that the commercially available diamine (137) is an excellent chiral acid (Scheme 28a).281 Although the process (& )-(136)-+ (R)-(136) requires stoichiometric amounts of the amine (137) it may be recovered unchanged by simple acid-base extraction. Similarly Kemps’ acid-derived imide (138) acts as a chiral 267 D. Toste J. McNulty and I. W. J. Still Synth. Commun. 1994 24 1617. 268 J. E. Macor B. L. Chenard and R. J. Post J. Org. Chem. 1994 59 7496. 269 Y. Nishiyama N. Shintomi Y.Kondo and Y. Okada J. Chem. Soc. Perkin Trans. 1 1994 3201. 270 A. P. Davis and J. J. Walsh Tetrahedron Lett. 1994 35 4865. 271 L. Singh and R.N. Ram J. Org. Chem. 1994 59 710. 272 T. Johnson and M. Quibell Tetrahedron Lett. 1994 35 463. 273 P. Breuilles R. Leclerc and D. Uguen Tetrahedron Lett. 1994 35 1401. 274 W. D. McGhee and Y. Pan and J. J. Talley Tetrahedron Lett. 1994 35 839. 275 K. Burgess and A.M. Porte Angew. Chem. Int. Ed. Engl. 1994 33 1182. 276 J. M. Seco S. Latypov E. Quiiioa and R. Riguera Tetrahedron Lett. 1994 35 2921. 277 T. Kusumi H. Takahashi P. Xu T. Fukushima Y. Asakawa T. Hashimoto Y. Kan and I. Inouye Tetrahedron Lett. 1994 35 4397. 278 L. Streinz A. Svatos J. Vrkoc and J. Meinwald J. Chem. Soc. Perkin Trans. 1 1994 3509.279 Y.Fukushi C. Yajima and J. Mizutani Tetrahedron Lett. 1994,35 599. I. Fleming and S. K. Ghosh J. Chem. Soc. Chem. Commun. 1994 99. E. Vedjes N. Lee and S.T. Sakata J. Am. Chem. Soc. 1994 116 2175. Synthetic Methods 3 19 Scheme 27 proton source for the asymmetric protonation of enolates (Scheme 28b).282 Enan- tioselective and catalytic protonation of enolates can be achieved using a catalytic amount of N-isopropyl ephedrine (140) via regeneration of the alcohol by deprotona- tion of phenyl-Zpropanone (Scheme 28c).283 In this manner the enolate of (& )-(139) is reprotonated by the ephedrine derivative (140) (0.5eq.) with very impressive enan- tioselectivity (98% e.e.). The selective fluorination of organic compounds continues to occupy the attention of many chemists; reviews describing the chemistry of fluorinated organometallic reagents284 and developments of fluorinating agents285 have appeared this year.The commonly encountered transformation of CO -,CF may be achieved efficiently by reaction of the corresponding azine oxime methyl ether or hydrazone derivative of the ketone with BrF3.286 The new electrophilic fluorinating agent (141) Se- lectfluorTM a stable commercially available and convenient source of F+ has seen several uses this year. It has been used to effect the methoxyfluorination of indole derivatives;287 fl-fluorination of aryl-alkyl substituted tertiary alcohols;288 mono and difluorination of 1,3-dicarbonyl compounds;289 and the oxidation of benzylic alcohols.290 Regiospecific fluorination of arenes (142) -,(143) (Scheme 29) may be achieved with the electrophilic fluorinating agent N-benzenesulfonimide (144) uiu directed ortho metallati~n.~~’ On the other hand cobaltocenium fluoride generated ’” A.Yanagisawa T. Kuribayashi T. Kikuchi and H. Yarnarnoto Angew. Chem. Int. Ed. Engl. 1994 33 107. 283 C. Fehr and J. Galindo Angew. Chem. Int. Ed. Engl. 1994 33 1888. 284 D.J. Burton Z.-Y. Yang and P. A. Morken Tetrahedron 1994 50 2993. ’” T. Umernoto Reo. Heteroatom Chem. 1994 10 123. 286 S. Rozen E. Mishani and A. Bar-Hairn J. Org. Chem. 1994 59 2918. ’13’ H. F. Hodson D. J. Madge A. N. Z. Slawin D. .A. Widdowson and D.J. Williams Tetrahedron 1994,50 1899. ’” S. Stavber and M. Zupan J. Chem. Soc. Chem. Commun.1994 149. 289 R. E. Banks N. J. Lawrence and A. L. Popplewell J. Chem. SOC.,Chem. Commun. 1994 343. 290 R. E. Banks N. J. Lawrence and A. L. Popplewell SYNLETT 1994 831. 291 V. Snieckus F. Beaulieu K. Mohri W. Han C. K. Murphy and F.A. Davis Tetrahedron Lett. 1994,35 3465. N. J. Lawrence Ph i MeLi ii 138 1.2 eq.. -78'C' a**'**''' 95% 87% e.e. (138) SPh ii,i (140) Bu"Li(0.5 eq.) k'SPh )y!yPh iii phy Me OH (*)-(139) 0 (s)-139 81% 98% e.e. Scheme 28 Scheme 29 Synthetic Methods 321 from cobaltocene and perfluorodecalin provides a useful source of ‘naked’ F-fluoride ion.292 Finally a solution to an old problem of organic chemistry the removal of water from a reaction. Stille and coworkers describe a newly designed apparatus a Dean-Stark- like trap that facilitates efficient azeotropic removal of water from a reaction mixture by adsorption of water by molecular sieves placed in a suitably designed trap.293 292 B.K.Bennett R.G. Harrison and T.G. Richmond J. Am. Chem. SOC. 1994 116 11 165. 293 N. S. Barta K. Paulvannan J.B. Schwarz and J. R. Stille Synth. Commun. 1994 24 583.

ISSN:0069-3030    

DOI:10.1039/OC9949100289

出版商:RSC    

年代:1994

数据来源: RSC

摘要:

10 Enzyme Chemistry By S. J. FAULCONBRIDGE K. E. HOLT J.S. PARRATT" S. P. SAVAGE and S. J. C. TAYLOR Chiroscience Ltd. 283 Cambridge Science Park Milton Road Cambridge CB4 4 WE UK 1 Introduction Academic and industrial researchers in the field of organic chemistry are faced with increasingly complex and sophisticated targets to synthesize. In particular the requirement for control of chirality and selective manipulation of similar functional groups frequently necessary under mild conditions encourages the synthetic chemist to explore every opportunity available. Biotransformations represent an important area in the set of methodologies available though a total review of the field is now only realistic in book form. A particularly useful review in this respect was written by Wong and Whitesides,' who tackled the subject from an applied and practical point of view.It is the intention of this review to follow in the footsteps of previous Annual Reports covering enzyme chemistry such as those written by Sutherland.2 Thus this report is broadly divided into the various types of enzyme-catalysed reaction highlighting biotransformations which fulfil the requirements above namely stereo- regio- and chemoselective reactions. 2 Hydrolysis and Condensation Reactions Transesterification of Complex Alcohols and Acids.-The most studied area of biotransformations is still lipase-catalysed hydrolysis and transesterification reactions. Routinely chemists can produce a wide range of low molecular weight enantiopure synthons using such technology.The regio- and stereoselective properties of these enzyme processes are exemplified by Pseudornonas cepacia lipase (Amano Lipase PS) (Scheme l) which was shown to transesterify both diols (1)3 and (2)4 in organic solvent. Such examples typify enzymic resolution technology widely reported in the literature. Other synthetically useful processes include the kinetic resolution of substituted 1,2-diols (Scheme 2). The aryloxy diol (3) was resolved using Lipase PS by an initial non-stereoselective acetylation of the primary hydroxy function followed by a C.-H. Wong and G.M. Whitesides 'Enzymes in Synthetic Organic Chemistry' Tetrahedron Organic Chemistry Series Volume 12,Elsevier Oxford UK,1994. A.G. Sutherland Ann. Rep. Prog.Chem. Sect. B Org. Chem. 1993,90 299. D.M.Coe A. Garofalo S. M. Roberts R. Storer and A. J. Thorpe J. Chem. SOC.,Perkin Trans. I 1994 3061. M.P.Sibi and J.-L. Lu Tetrahedron Lett. 1994,35 4915. 323 S.J. Faulconbridge et al. -q I OAc OAc (72% e.e.) (95% e.e.) li ?f -(R,R) 88% 8.e. (S,S)78%8.8. (S,S)>99% 8.8. 50% yield 21% yield 29% yieM Reagents:i Lipase PS vinyl acetate 30 "C,26 hours; ii Lipase PS vinyl acetate hexane room temperature 24 hours Scheme 1 94% 8.8. (R)96% e.e. (S) 48% yield 52% yield PhLph 2 /Ph .. PhYT + HO OH HO OH HO OAc (*I441 (S)~99%e.e. (R)93% 8.8. Reagents i Lipase PS vinyl acetate THF/NEt, 28 hours (E > LOO); ii Pseudomonas sp. vinyl acetate diisopropyl ether 2 days room temperature (E > 200) Scheme 2 sequential and highly S-selective acetylation of the secondary alcoh01.~ In contrast the resolution of the a,a-disubstituted diol(4) was achieved by an R-selective esterification specifically at the primary hydroxyl catalysed by Pseudomonas sp.lipase.6 The second F. The& J. Weidner S. Ballschuh A. Kunath and H. Schick J. Org. Chem. 1994 59 388. R. P. Hof and R. M. Kellogg Tetrahedron Asymmetry 1994 5 565. Enzyme Chemistry example illustrates a method for generating optically active tertiary alcohols which are regarded generally as being troublesome compounds to obtain directly. The use of lipases in organic solvents has also been extensively studied with regard to the resolution of monohydroxy compounds.The exploitation of such methodology allows access to homochiral synthons which have applications in the synthesis of important pharmaceutical agents such as carbovir7 and teleomycin antibiotim8 PseudomonasJIuorescenslipase was also shown to be of use in the synthesis of the much studied (R)-and (S)-mevalonolactone [by resolution of the racemic 2-(3-methylbut-2- enyl) oxiranemethanol intermediateJg as well as in the resolution of glycerol-2,3-carbonate (a C synthon of much potential)." With the emphasis placed on hydantoinase-catalysed resolution of racemic hydantoin moieties it is refreshing to note that this is not the only methodology of use in this area. A lipase-catalysed transacetylation of 5,5-disubstituted hydantoins has also been described (Scheme 3).' Although the selectivity of the reaction is only moderate this is still an interesting approach to the formation of optically active a,a-disubstituted amino acids.(R)80% 8.8. 31% yield (S)43% 8.8. 56% yield Reagents i Pseudomonas sp. vinyl acetate 5 hours acetonitrile 0 "C scheme 3 Biotransformations are still finding a useful role within the realms of organometallic chemistry. Moreover lipases have been shown to be most effective as catalysts for the kinetic resolution of planar-chiral ferrocenes in transesterification mode.' Such resolutions tend to make use of hydroxymethyl groups situated on unsaturated ligands as illustrated in Scheme 4. In this example Pseudomonas sp. lipase catalyses the acetylation reaction using isoprenyl acetate to resolve the racemic chromium species (5) with extremely high selectivity (E > 500).13 The transesterification of complex acids has also been an area of research widely investigated with many diverse substrates being utilized.Much of this effort has focused upon the area of 2-arylpropionic acid resolution with a view to producing the well known Profen family of antiinflammatory drugs. 14*1 The regioselective behav- iour of lipases towards complex acid moieties has also been explored with one spectacular example being the enzyme-mediated synthesis of diester crown ethers. ' H. Nakano Y. Okuyama K. Iwasa and H. Hongo Tetrahedron Asymmetry 1994 5 1155. H. Sundram A. Golebiowski and C. R. Johnson Tetrahedron Lett. 1994,35 6975. P. Ferraboshi P. Grisenti S.Casati and E. Santaniello SYNLETT 1994 754. lo M. Pallavicini E. Valoti L. Villa and 0.Piccolo J. Org. Chem. 1994 59 1751. '' E. Mizuguchi K. Achiwa H. Wakamatsu and Y. Terao Tetrahedron Asymmetry 1994 5 1407. G. Nicolosi A. Patti R. Morrone and M. Piattelli Tetrahedron Asymmetry 1994 5 1275 l3 M. Uemura H. Nishimura S. Yammada and Y. Hayashi Tetrahedron Asymmetry 1994 5 1673. l4 M. Arroyo and J. V. Sinisterra J. Org. Chem. 1994 59 4410. S.-W. Tsai and H.-J. Wei Enzyme Microb. Technol. 1994 16 328. S.J. Faulconbridge et al. (1R ,2S)>99% 8.8. (1S,2R)98%e.e. 47% yield 48% yield Reagents i Pseudomonas sp. lipase 25 "C 3 hours isoprenyl acetate Scheme 4 Polyethylene Recovered Acyclic Cyclic glycol (6) (8a)-(8c)% (9a)-(9c)% (7a) n = 1 57 12 9 (7b) n = 2 14 3 5 (7~) n = 3 42 7 7 Reagents i Mucor miehei lipase toluene 6O"C 12 days Scheme 5 Conde and coworkers employed Mucor miehei lipase together with a range of polyethylene glycol nucleophiles (7at(7c) to transesterify 1,3-bis(3,5-diethoxycar-bonyl- 1H-pyrazol-1-y1)propane (6) (Scheme 5).16 Despite the poor isolated yields of (8at(8c) and (9at(9c) notable regiocontrol is exhibited with no byproducts detected when using nucleophiles (7b) and (7c) and less than 1 YOisolated when the reaction was l6 M.Fierros M. I. Rodriguez-Franco P. Navarro and S. Conde Bioorg.Med. Chem. Lett. 1994,4,2523. Enzyme Chemistry MeoXco2Me H C02Me Reagents i CCL hexane 3.5 hours 40 "C,BnOH (53% conversion); ii H,/Pd toluene/hexane; iii BH, THF Scheme 6 performed with (7a).Such biocatalytic methodology is far from well characterized; however such examples can only encourage enzymic methodology for the preparation of macromolecules in the future. Shapira and Gutman reported a strategy for the formation of a series of hitherto unknown chiral monosubstituted malonate diesters via a lipase-mediated transes- terification of the corresponding prochiral dimethyl malonate esters. Candida cylin-dracea lipase (CCL),with benzyl alcohol as the nucleophile provided the best results in terms of product e.e. when using the methoxy malonate (10) (Scheme 6).17The solvent of choice was hexane selected for its well-known compatibility with enzymes and its high hydrophobicity minimizing the lability of the malonic hydrogen (thus reducing undesirable product racemization).This approach also allowed for the isolation of the unstable malonate half ester (12) easily effected by the catalytic hydrogenation of the benzyl ester (1 1). Further synthetic manipulation accessed the hydroxy ester (13) with an e.e. of 70%. The adaptation of reversible enzyme reactions to provide irreversible processes has been reviewed with particular reference to strategies applicable to the synthesis not only of esters but also of peptides nucleosides and carbohydrates." However another publication examined the use of mixed carboxylic carbonic anhydrides as irreversible acyl transfer reagents for the lipozyme-catalysed resolution of carboxylic acids.'' Such acyl transfer reactions were reported to be rapid (20 minutes to 2 hours) and due to the liberation of carbon dioxide the equilibrium position was shifted completely towards the products (Scheme 7).Furthermore the other side product isopropanol is apparently inert towards side reactions such as subsequent trans- esterification of the ester product. 0 0 0 R\roYop+ + PrOH ,-f+ phpopr + Pr'OH Me co2 Me 90% 8.8. (E = 20) (absolute stereochemistry not reported) Reagents i Lipozyme room temperature Bu'OMe 60 minutes 55% conversion Scheme 7 M. Shapira and A. L. Gutman Tetrahedron Asymmetry 1994 5 1689. J.-M. Fang and C.-H. Wong SYNLETT 1994 393. l9 E. Guibe-Jampel and M. Bassir Tetrahedron Lett. 1994 35 421. S.J. Faulconbridge et al.-i Et02C CO2Et H02C CO2Et Reagents i PLE pH 7.8 27 "C Scheme 8 Ad Ad ,Ph i t 0gPh 0g" -(14) (i)cis (3R,2S)acetate>99°/o8.8. (3S,2R)alcohol>99?h e.e. Reagents i Lipase PS/Lipase BMS (Bristol-Myers Squibb) Scheme 9 Hydrolysis of Complex Acids and Alcohols.-A worthy example of the versatility of lipase enzymes in the hydrolytic mode was reported by Adamczyk et aL2* Both benzyl and methyl esters of rapamycin 42-hemisuccinate were cleaved under mild conditions using Pseudomonas sp. lipase. Indeed it was claimed that the deprotection of benzyl esters in the presence of other easily reducible groups could well be considered equivalent to a selective reduction. Such mild hydrolytic conditions coupled with the the fact that peptide linkages are inert to lipase attack have also found application within the realms of glycopeptide chemistry.2 The useful regioselectivity of lipases was demonstrated in the hydrolysis of diethyl itaconate to the monoester (Scheme 8);22 chemical esterification of itaconic acid gave the regioisomer.Enzymes are increasingly being used by pharmaceutical companies for the synthesis of key intermediates (Scheme 9).23The azetidinone (14) is an intermediate in the synthesis of the anticancer compound paclitaxel (Taxolo). Immobilization of the lipase on polypropylene facilitated reuse of the enzyme for ten successive cycles without loss of activity or selectivity. Hydrolases continue to appear from unusual sources thus providing alternatives to the available set of commercial lipases (Scheme A variety of homochiral trans-2-arylcyclohexan- 1-01s were thus synthesized using crude chicken liver esterase.The creation of a sole centre of chirality on a heteroatom in good e.e. has been reported (Scheme 1 l).25In this example the prochiral sulfoxides (15) and (16) were converted into the ester acids (17) and (18) respectively. In the case of (17) the absolute 2o M. Adarnczyk J. C. Gebler and P. G. Mattingly Tetrahedron Lett. 1994 35 1019. 2' H. Kunz D. Kowalczyk P. Braun and G. Braurn Angew. Chem. Int. Ed. Engl. 1994 33 336. 22 P. Ferraboschi S. Casati P. Grisenti and E. Santaniello Tetrahedron 1994 50 3251. 23 R. N. Patel A. Banerjee R. Y. KO,J. M. Howell W.-S. Li F.T. Comezoglu R. A. Partyka and L. Szarka Biotechnol.Appl. Biochem. 1994 20 23. 24 D. Basavaiah and P. Dharrna Rao Tetrahedron Asymmetry 1994 5 223. 25 M. Mikolajczyk P. Kielbasinski R. Zurawinski W. Wieczorek and J. Blaszczyk SYNLETT 1994 127. Enzyme Chemistry Ar Ar Ar = phenyl 1-naphthyl >99% e .e . 4-met hylphenyl 2,4,64rimethylphenyl Reagents i Crude chicken liver esterase Scheme 10 (15) (R)-(17) 9290 e.e. 63% yieM (16) (R)-(18) 67% e.e. 70% yield Reagents i cr-chymotrypsin 16 hours pH 7.5; ii PLE 40 hours pH 7.5 Scheme 11 A& 0 + I &!\Ph Me U MPh e (S)-(19) 49% 8.8. (R)-(20)53% 8.8. 0 ! -11 I1 ! MeO-P-We MeO-P-OH + MeO-P-SMe I I I NHCOMe NHCOMe NHCOMe (achiral) Reagents i Cholesterol esterase; ii Phosphotriesterase from Pseudomonas diminuta or Flauobacterium sp.Scheme 12 stereochemistry was successfully established by single crystal X-ray diffraction. Compounds containing a phosphorus stereocentre have also been obtained using hydrolytic enzymes (Scheme 12). Hence (+)-(19) was resolved uia a cholesterol esterase-catalysed hydrolysis of the remote acetate functionality yielding the pheno1 S.J. Faulconbridge et al. (4(22) (23)61% 8.8. (22) 18% 8.8. Reagents i CCL 34 hours 40% conversion Scheme 13 i R (24) R = H (25) R=NOp Reagents i fi-glucosidase Scheme 14 (R)-(20).26 In an alternative approach phosphotriesterase was found to hydrolyse the P-S bond S-selectively in the organophosphate triester ( & )-(21).27 The resolution of tertiary alcohols has been explored using Candida cylindracea lipase.The racemic t-acetylenic alcohol (22) was resolved by hydrolysing the acetate function (Scheme 13) albeit with poor e.e. to furnish the t-alcohol (23).28 Glycosidation Reactions.-A wide variety of glycosides have been synthesized using P-glycosidases and transfera~es.~’~~ The diastereoselective cleavage of sulfoxides (24) and (25) was demonstrated using P-glycosidases (Scheme 14).32 This represents the first example of the diastereoselective hydrolysis of sulfoxides by an enzyme and gave diastereoisomerically pure recovered sulfoxides. An elegant synthesis of aleppotriolo-side a naturally occurring glucoside was achieved in which the two key reactions were a Pseudornonas JEuorescens-catalysed enantioselective resolution and transglucosyla- tion of the intermediate by a thermophilic P-glycosidase from Sulfolobus solfutaricus (Scheme 15).33 Nitrile and Epoxide Hydrolysis.-Interest in biocatalytic nitrile hydrolysis is growing steadily.The area has been spotlighted as a mini review in a keynote article by Turner 26 A.N. Serreqi and R. J. Kazlauskas J. Org. Chem. 1994 59 7609. 2’ M.-Y. Chae J. F. Postula and F. M. Raushel Bioorg. Med. Chem. Lett. 1994 4 1473. 28 D. O’Hagan and N. A. Zaidi Tetrahedron Asymmetry 1994 5 11 11. 29 W. H. Binder H. Kahlig and W. Schmid Tetrahedron 1994 50 10407. ’O A. Baker N. J. Turner and M. C. Webberley Tetrahedron Asymmetry 1994 5 2517. G.F. Herrmann P. Wang G.-J. Shen and C.-H. Wong Angew. Chem. Int. Ed. Engl.1994 33 1241. 32 0.Karthaus S. Shoda and S. Kobayashi Tetrahedron Asymmetry 1994 5 2213. 33 A. Trincone E. Pagnotta and G. Sodano Tetrahedron Lett. 1994 35 1415. Enzyme Chemistry 331 OAc OAc OH \0' HO*LG HO '* OH aleppotridoside Reagents i Pseudomonas fluorexens lipase pH 7 6 days; ii CH,MgBr Et,O; iii Sulfolobus solfataricus homogenate phenyl-fl-D-glucoside Scheme 15 and coworkers.34 Also reported here were the first examples of biocatalytic regioselective nitrile hydrolysis effected by an immobilized whole-cell preparation (derived from Rhodococcus sp.) containing both nitrile hydratase and amidase enzymes. As Scheme 16 illustrates both hydrolytic reactions proceed selectively to the nitrile-amide compounds (28) and (29) with no other products detected.Interestingly the non-fluorinated analogues of (26) and (27) were biotransformed with little or no regiocontrol and furthermore the products observed were nitrile-acids and not nitrile-amides. Other groups working in this field have further investigated the enantioselectivity of nitrile biohydrolysis. Racemic 2-arylpropionitriles have been studied using enriched bacterial isolates; such methods include a highly selective process for the synthesis of enantiopure (S)-napr~xen.~~.~~ Furthermore Knowles and coworkers demonstrated the enantioselective behaviour of a nitrilase enzyme from R. rhodochrous that catalyses the single step process of transforming nitriles directly into carboxylic acids. Both racemic 2-methylbutyronitrile and 2-methylhexanitrile were hydrolysed to their corresponding carboxylic acids in an S-selective fashion and with high e.e.37,38 The 34 J.Crosby J. Moilliet J. S. Parratt and N. J. Turner J. Chem. Soc. Perkin Trans. I 1994 1679. 35 R. Bauer B. Hirrlinger N. Layh A. Stolz and H.-J. Knackmuss Appl. Microbiol. Biotechnol. 1994,42 1. 36 N. Layh A. Stolz J. Bohme F. Effenberger and H.-J. Knackmuss J. Biotechnol. 1994 33 175. 37 M.L. Gradley C. J. F. Derverson and C.J. Knowles Arch. Microbiol. 1994 161 246. 38 M. L. Gradley and C.J. Knowles Biotechnol. Lett. 1994 16 41. S.J. Faulconbridge et al. Reagents i Nitrilase SP361 phosphate buffer 7G115 hours 30 "C Scheme 16 OH (S)-(31) >90% e.8. AN3 (R)-(32),>60% 8.8. Reagents i SP409 TRIS buffer N; room temperature Scheme 17 enantioselective potential of biocatalytic prochiral 3-0-substituted glutaronitrile hydrolysis has been further reported this year with the production of enantiomerically pure (S)-cyano-acids using Brevibacteriurn SP.~' Faber et al.have continued their investigations into the use of an immobilized whole-cell preparation SP409 derived from Rhodococcus sp. to effect enantioselective epoxide hydr~lysis.~' The racemic epoxide (30) (Scheme 17) was exposed to the biocatalyst in the presence of azide to form both the (S)-diol(31) (>90% e.e.) and the (R)-azido-alcohol (32) (>60% e.e.). Careful monitoring of the reaction in terms of optical purities of the reaction components against time led to the conclusion that the epoxide ring-opening by azide was enzyme catalysed and was not a spontaneous 39 A.Kerridge J. S. Parratt S. M. Roberts F. Theil N. J. Turner and A. J. Willetts Bioorg. Med. Chem.,1994 2 447. 40 M. Mischitz and K. Faber Tetrahedron Lett. 1994 35 81. Enzyme Chemistry 333 reaction. No conclusions were drawn however as to whether the epoxide hydrolase accepted azide as a nucleophile or if another enzyme was involved. Other work reported in this field includes the exploitation of cytosolic and microsomal epoxide hydrolases from rabbit liver.41 It was demonstrated that microsomal epoxide hydrolase was able regio- and enantioselectively to ring open both styrene oxide and trans- 1-phenylpropene oxide at the non-benzylic oxirane carbon.However in contrast cytosolic epoxide hydrolase effects a non-selective hydrolytic attack of styrene oxide and a regioselective but non-enantioselective reaction at the benzylic carbon of trans-1-phenylpropene oxide. Amide Hydrolysis and Condensation.-The ability of enzymes to hydrolyse amide functionalities has been further de~cribed.~~,~~ However the much-studied penicillin acylase still appears to be at the forefront with regard to synthetic versatility. The substrate specificity of microbial penicillin acylase towards a variety of N-phenylacetyl-P-fluoroalkyl-P-aminoacids has been in~estigated.~~ The results pub- lished suggested that the high level of enantioselectivity exhibited was not influenced by the length of the fluoroalkyl chain.In contrast however it was reported that modification of the phenylacetyl moiety at the a-position with a range of different substituents does affect the activity of immobilized penicillin-(; acylase towards penicillin and cephalosporin derivative^.^^ Furthermore the insertion or removal of atoms between the aromatic nucleus of the phenylacetyl fragment and the centre of hydrolysis lead to molecules which are no longer substrates for the enzyme. The continued use of Alcalase a proteolytic catalyst whose major component is subtilisin Carlsberg in peptide synthesis has yielded some significant results particularly in the preparation of a variety of biologically active intermediate^.^^.^^ The thiol protease papain has also been utilized with Sih and coworkers employing 5(4H)-oxazolinones as acyl donors in the synthesis of peptide segments.48 This methodology brought about the successful coupling of the oxide insulin B chain to angiotensin I11 in an impressive 59% yield.3 Reduction Reactions Wholecell Reductions.-The enantioselective conversion of ketones into chiral alcohols continues to be the most active domain in whole-cell reductions where bakers’ yeast remains the most popular choice of biocatalyst. Buisson et al. observed high diastereoselectivity and enantioselectivity in reduction of the a-substituted /3-ketoester (33) with a selection of microorganisms (Scheme 18). In most cases cis:trans ratios of the product (34) were reported to exceed 99 1. The (1R,2R)-enantiomer was produced by fungal strains such as Mucor racemosus Rhizopus 41 G.Bellucci C. Chiappe A. Cordoni and F. Marioni Tetrahedron Lett. 1994 35 4219. 42 B. Kaptein H. M. Moody Q. B. Broxterman and J. Kamphuis J. Chem. Soc. Perkin Trans. I 1994 1495. 43 J. Ogawa M.C.-M. Chung S. Hida H. Yamada and S. Shimizu J. Biotechnol. 1994 38 11. 44 V.A. Soloshonok A.G. Kirilenko N. A. Fokina I. P. Shishkina S.V. Galushko V. P. Kukhar V. K. Svedas and E. V. Kozlova Tetrahedron Asymmetry 1994 5 11 19. 45 M. van der Mey and E. de Vroom Bioorg. Med. Chem. Lett. 1994 4 345. 46 S.-T. Chen S.-Y. Chen C.-L. Kao and K.-T. Wang Biotechnol. Lett. 1994 16 1075. 4’ S.-T. Chen S.-Y. Chen C.-L. Kao and K.-T. Wang Bioorg. Med. Chem. Lett. 1994,4,443. 48 B.K. Hwang Q.-M. Gu and C. J. Sih Tetrahedron Lett.1994 35 2317. S.J. Faulconbridge et al. 0 OH (33) (34) Scheme 18 (35) (36)72% yield Reagents i Bakers' yeast Scheme 19 0 0 X X X = Halogen NO2,CHO COCH3 COPh Reagents i Bakers' yeast NaOH H,O-MeOH 7G80 "C Scheme 20 arrhizus and Sporotrichum exile in >99% e.e. In contrast the complementary enantio activity was demonstrated by bakers' yeast affording the (lS,2S)-enantiomer in >95% e.e.49 A topic of current therapeutic interest is the synthesis of paclitaxel a compound possessing significant antitumour activity. A precursor of its C-13 side chain (2R,3S)-phenylisoserine (36) has been prepared by bakers' yeast reduction of the a-ketoester (35) furnishing the correct stereochemistry at the new chiral centre (Scheme 19).50 In addition to the synthesis of chiral alcohols bakers' yeast enjoys widespread application to a host of other reductions.One such reaction is the reduction of aromatic nitro compounds an area which has attracted only limited study. Baik et al. report selective reduction of substituted nitrobenzenes to the corresponding anilines (Scheme 20).51 In examples where the substituent contains carbonyl functionality (e.g. X = CHO COMe COPh) the amino derivative was selectively obtained in high yield without further carbonyl reduction. 49 D. Buisson R. Cecchi J. A. Laffitte U. Guzzi and R. Azerad Tetrahedron Lett. 1994 35,3091. J. Kearns and M. M. Kayser Tetrahedron Lett. 1994 35,2845. '' W.Baik J. L. Han K.-C. Lee N.-H. Lee B.-H. Kim and J.T. Hahn Tetrahedron Lett.1994 35,3965. Enzyme Chemistry Bakers' yeast 56% 10% Enzyme Enzyme NADH NAD' 1 Scheme 21 (41a) R=H (42a) R= H (43a) R = H (41b) R=Me (42b) R = Me (43b) R=Me Reagents i Bakers' yeast 7G72 hours 33 "C Scheme 22 Interestingly in a parallel study bakers' yeast reduction of 2-nitrobenzonitrile (37) furnished 2-aminobenzamide (38) as the major product. The mechanism (Scheme 21) postulated involved initial reduction to the oxime (39) followed by intramolecular attack of the hydroxyl group onto the nitrile (40). A subsequent two-electron reduction of (40) would furnish the benzamide (38).52 Reduction of the (E)-nitrophenyl nitroalkenes (Scheme 22) also catalysed by bakers' yeast demonstrated a degree of chemoselectivity dependent upon the nitroalkene substituent R.The substrate (41a) produced almost exclusively the nitroalkane (42a). In contrast where the substituent was methyl (41b) the aniline derivative (43b) was obtained in preference to the nitroalkane (42b).53 The unsaturated b-lactone (44) underwent kinetic resolution with bakers' yeast supplying (+ )-(R)-(44) in 99% e.e. (Scheme 23). Mechanistic considerations based on analogous work proposed hydride delivery in the /?position from the upper re face of the lactone framework affording selective reduction of the S enanti~mer.~~ 52 C. L. Davey L. W. Powell N. J. Turner and A. Wells Tetrahedron Lett. 1994 35,7867. 53 M. Takeshita S. Yoshida and Y. Kohno Heterocycles 1994 37 553. 54 C. Fuganti G. Pedrocchi-Fantone A.Sarra and S. Servi Tetrahedron Asymmetry 1994 5 1135. S.J. Faulconbridge et al. (44) (R)-(44),99% e.e. Reagents i Bakers' yeast D-glucose 36 "C,DMSO 6 hours Scheme 23 i C02Et -4-"CO2Et (45) (46)100%e.e Reagents i Enzyme from Catharanthus roseus NADPH Scheme 24 (47) (48) 97V0e.e. Reagents i DMSO reductase benzyl viologen 25 "C Scheme 25 Isolated-enzyme Reductions.-On the whole most isolated reductases have been extracted from either animal tissue or microbes while enzymes from plant cell cultures are comparatively rare. One such enzyme purified from the membrane portion of Catharanthus roseus reduced the cr-keto ester (45) enantioselectively to the (R)-cr-hydroxy ester (46) in 100% e.e. (Scheme 24).5s A DMSO reductase from a mutant of Rhodobacter sphaeroides f.s.denitrijcans exclusively reduced the (S)-sulfoxide (47) to its sulfide (Scheme 25) leaving the optically active R enantiomer (48).56 The development and application of reductions effected by isolated enzymes continue to be hindered by cofactor recycling. Traditionally this problem has been tackled albeit inefficiently by enzymic or chemical means. Another approach involves direct electrochemical regeneration of the cofactor a method which suffers from the formation of isomers and dimers. Yun et al. however report a promising system for NADH regeneration employing a diaphragm composed of an anion-charged 55 H. Hamada N. Nakajima Y. Shisa M. Funahashi and K. Nakamura Bioorg. Med. Chem. Lett. 1994,4 907.56 M. Abo M. Tachibana A. Okubo and S. Yamazaki Biosci Biotech. Biochem. 1994 58 596. Enzyme Chemistry 337 membrane coupled with appropriate regulation of the cathodic potential. The system worked favourably as an NADH regenerator in a reaction involving lactate dehydr~genase.~’ An indirect electrochemical approach was developed by Fry et al. in which a long-term stable electroenzymatic system was prepared for NADH regeneration simply by coimmobilizing lipoamide dehydrogenase and a methyl viologen mediator on an electrode under a NafionO film. This approach is superior to a homogeneous two-enzyme system as both enzymes are separated and the biotoxic viologen is kept out of solution.58 4 Oxidation Reactions Biocatalytic oxidation of organic compounds (primarily of carbon or sulfur) is becoming an increasingly useful methodology in organic synthesis.Although most examples target the introduction of chirality useful regioselective oxidations have been noted. Baeyer-Villiger oxidation of ketones is an important transformation for lactone synthesis. The Baeyer-Villiger oxidation of monocyclic and bicyclic ketones by Acinetobacter calcoaceticus NCIMB 987 1 and Pseudomonas putida NCIMB 10007has been studied in some detail.59 For example Acinetobacter calcoaceticus oxidized the racemic dihalogenoketone (49) to optically active lactone (50) and recovered ketone (51) (Scheme 26). The ketone was converted in seven steps to an azidothymidine (AZT) analogue (52). The microbial dioxygenation of substituted benzenes to produce homochiral cis-dihydrodiols has long been recognized and examples of the use of these diols in organic synthesis continue to appear in the literature.Thus a recent example is the chemoenzymatic synthesis of D-erythro-C *-and L-threo-C 8-sphingosines,60 which when combined with carbohydrates and fatty acids constitute glycosphigolipids. These are of much interest due to their diverse biological roles such as protein kinase C inhibition and information transfer agents between developing vertebral cells. The cyclohexadiene-cis-diol from chlorobenzene was used to synthesize (53) and (54) precursors for (55) and (56) (Scheme 27). Selective oxidative metabolism of racemic compounds by microorganisms has been frequently used for the provision of chiral molecules.Thus exposure of Candida parapsilosis to butane- 1,3-diol allowed accumulation of multikilo quantities of (R)-(-)-butane-1,3-diol (Scheme 28).61 Whole cell oxidation of several prochiral diols by Nocardia corallina (Scheme 29) resulted in the formation of chiral lactones of high optical purity.62 In all the examples cited the products were derived from the oxidation of the pro-S hydroxymethylene group. The biotransformation of racemic mandelic acid by a mutant of Pseudomonas putida 57 S. Yun M. Taya and S. Tone Biotechnol. Lett. 1994 16 1053. A. J. Fry S. B. Sobolov M. D. Leonida and K.I. Voivodov Tetrahedron Lett. 1994 35 5607. 59 R. Gagnon G. Grogan M. S. Levitt S. M. Roberts P.W. H. Wan and A. J. Willetts J.Chem. SOC. Perkin Trans. I 1994 2537. 6o T. Hudlicky T. Nugent and W. Griffith J. Org. Chem. 1994 59 7944. 61 A. Matsuyama and Y. Kobayashi Biosci. Biotech. Biochem. 1994 58 1148. 62 H. Luna K. Prasad and 0.RepiE Tetrahedron Asymmetry 1994 5 303. S.J. Faulconbridge et al. (49) (50) (511 e.e.>95% 40% yield e.e.>95% 40% yield 7 steps 1 F Reagents i A. calcoaceticus NCIMB 9871 Scheme 26 OH (53) (55) (Scheme30),defective in muconolactone isomerase provided the highly functionalized muconolactone 5-carboxymethyl-2,5-dihydrofuran-2-one in high enantiomeric purity (97% e.e.).63 D. W. Ribbons and A. G. Sutherland Tetrahedron 1994 50 3587 Enzyme Chemistry 94% 8.8. Reagents i Candida parapsilosis Scheme 28 >!39% 8.8.OH OH 95% 8.8. Reagents i Nocardia Corallina Scheme 29 Reagents i muconate cycloisomerase; ii muconolactone isomerase Scheme 30 Microbial oxidation of sulfur for the preparation of chiral sulfoxides continues to attract interest.64 The fungus Helminthosporiurn species NRRL 467 1 was used to 64 H. L. Holland F. M. Brown and B. G. Larsen Tetrahedron Asymmetry 1994 5 1241. S.J. Faulconbridge et al. R = Me Et Pr" Bun (S) 52435% e .e. 42-70%yield Reagents i Helminthosporium NRRL 4671 Scheme 31 Reagents i Pseudomonas acidovorans Scheme 32 biotransform a series of para-alkylbenzyl sulfides (Scheme 3 1) giving moderate yields of sulfoxides with predominantly S chirality at sulfur. Lower yields of the sulfones were also reported.Regiospecific hydroxylation of pyrazine carboxylic acids gives compounds for synthesis of pharmaceutically active substances such as Glipicide an antidiabetic or Pyrazinamide a tuberculostatic agent.65 Of several biotransformations investigated the most promising was the hydroxylation of pyrazine carboxylic acid to 5-hydroxypyrazine-Zcarboxylic acid (Scheme 32). A product concentration of 75 g 1-' in 96% yield was obtained in 24 hours. 5 Carbon-Carbon Bond-forming Reactions The continuing interest in aza sugars and their analogues due to their antiviral and antitumour activities has resulted in several publications relating to their synthesis this year. These routes utilize aldola~e~~.~~ and transketolase68 enzymes to catalyse the key asymmetric aldol addition reaction (Scheme 33).A new route to deoxythiosugars based on aldolases has been de~eloped.~' The use of thioaldehydes as acceptors for fructose 1,6-diphosphate aldolase rhamulose 1-phosphate aldolase fuculose 1-phosphate aldolase and 2-deoxyribose 5-phosphate aldolase demonstrates the synthetic utility of these enzymes. Kragl et al. report new findings in the sialic acid aldolase-catalysed condensation of pyruvate with various sugar substrates (for an example see Scheme 34).70 An apparent relationship between 65 A. Kiener J.-P. Roduit A. Tschech A. Tinschert and K. Heinzmann SYNLETT 1994 814. 66 K. E. Holt F. J. Leeper and S. Handa J. Chem. SOC.,Perkin Trans. I 1994 231. 67 I. Henderson K. Laslo and C.-H.Wong Tetrahedron Lett. 1994 35,359. 68 L. Hecquet M. Lemaire J. Bolte and C. Demuynck Tetrahedron Lett. 1994 35,8791. 69 W.-C. Chou L. Chen J.-M. Fang and C.-H. Wong J. Am. Chem. SOC. 1994 114,6191. 'O U. Kragl A. Godde C. Wandrey N. Lubin and C. Auge J. Chem. SOC.,Perkin Trans. I 1994 119. Enzyme Chemistry 341 OH OH OH "Y, HO OH 1. I1 HOWOH iii_ GO H -N3 OH 0 OH 0 OEt 1 1 OH Reagents i Rabbit muscle aldolase dihydroxyacetone phosphate; ii acid phosphatase; iii 10% Pd/C H, 40 psi; iv BuLi dithiane; v HCI-KCI buffer pH l/EtOH (70/30); vi hydroxypyruvate transketolase Scheme33 OH HO OH O H -Ho9c02H WI HO HO OH HO Dallose Reagents i Sialyl aldolase pyruvate Scheme 34 enzyme stereoselectivity and conformation and stereochemistry at C-3of the substrate is discussed.The enzyme-catalysed asymmetric synthesis of cyanohydrins has been reviewed this year by Effenberger." Elsewhere Kiljunen describes the use of lyophilized powdered and washed Sorghum shoots as an (S)-oxynitrilase source thus eliminating the need for purification and immobilization of this enzyme (Scheme 35).72 71 F. Effenberger Angew. Chem. lnt. Ed. Engl. 1994 33 1555. 72 E. Kiljunen and L.T. Kanerva Tetrahedron Asymmetry 1994 5 311. S.J. Faulconbridge et al. CN I -0""" i c8. 90% yield 90% 8.8. Reagents i Acetone cyanohydrin Sorghum bicolor shoots diisopropyl ether Scheme 35 Antlbody <Ar > 98% 8.8. Scheme 36 86?4e.e. 1.5 g Reagents i H' antibody 20T pH 6 Scheme 37 6 Abzymes Since the first catalytic antibodies (abzymes) were reported in 1986,abzymes catalysing numerous types of reaction have been reported.This year has seen a large amount of literature on the subject including two review^.^^^^^ An interesting discovery by Koch et al. was the enantioselective epoxidation of unfunctionalized alkenes-the first report of an antibody-catalysed oxidation reaction at carbon (for an example see Scheme 36).75 In order for abzymes to be synthetically useful it is essential that their large scale use is possible. Thus Reymond et al. have reported the multigram hydrolysis of enol ether (57) using a reusable catalytic antibody and a very simple laboratory procedure (Scheme 37).76 73 G.M. Blackburn and P. Wentworth The Genetic Engineer and Biotechnologist 1994 14 9 74 H. Suzuki J. Biochem. 1994 115 623. 7s A. Koch J.-L. Reymond and R. A. Lerner J. Am. Chem. Soc. 1994 116 803. 76 J.-L. Reymond J.-L. Reber and R.A. Lerner Angew. Chem. Int. Ed. Engl. 1994,33 475.

ISSN:0069-3030    

DOI:10.1039/OC9949100323

出版商:RSC    

年代:1994

数据来源: RSC